HEALTH  SCIENCES  STANDARD 


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ANi^MIA. 


BY 


FREDERICK  P.  HENRY,  M.D., 

PROF.    OF    CLINICAL    MEDICINE    IN    THE    PHILADELPHIA     POLY- 
CLINIC;    ONE    OF   THE    PHYSICIANS  TO    THE    EPISCOPAL    HOS- 
PITAL;    ONE    OF   THE    PHYSICIANS    TO    THE    PHILADELPHIA 
HOSPITAL  ;    CONSULTING   PHYSICIAN   TO    THE    HOME    FOR 
CONSUMPTIVES  ;      CORRESPONDING     MEMBER      OF     THE 
ROYAL    MEDICAL    ACADEMY    OF    ROME,  ETC.,  ETC. 


REPRINTED    FROM 


THE    POLYCLINIC. 


PHILADELPHIA: 
P.   BLAKISTON,   SON   &   CO., 

No.  IOI2  Walnut  Street. 
1887. 


Copyright,  1887,  by 
P.  BLAKISTON,  SON  &  CO. 


DR.  S.  WEIR  MITCHELL, 

THIS   WORK    IS,    BY    PERMISSION,    RESPECTFULLY 
DEDICATED. 


"  Semper  honos,  nomenque  tuum,  laudesque  manebunt. 
Quae  me  cunque  terrae  vocant." 


PREFACE. 


This,  the  first  systematic  treatise  on  anaemia 
published  in  this  country,  is  a  reprint  of  a  series 
of  articles  published  in  The  Polyclinic  dur- 
ing the  past  year,  and  embodies  the  results 
of  many  years'  study  of  the  blood  and  the  dis- 
orders consequent  upon  its  imperfect  elabora- 
tion. The  statements  which  it  contains  are, 
for  the  most  part,  based  upon  personal  obser- 
vation, and  where  this  has  been  wanting,  upon 
accepted  facts  of  physiology  and  pathology. 
I  have  endeavored  to  supply  the  want  of  a 
trustworthy  guide  to  a  wide  and  growing  field 
of  research — a  want  which  I  myself  have 
keenly  felt. 

7^7  Pine  Street,  June  ist,  i88j. 


COiNTENTS. 


PAGH 

Introduction, I 

Methods  of  Examination, lo 

Anaemia  in  General, 15 

Exciting  Causes  of  Antemia, 20 

Symptoms  of  Anaemia, 27 

Anatomical  Characters  of  Ameiiiia, 30 

Diagnosis  of  Anaemia, 31 

Prognosis  of  Anaemia 34 

Treatment  of  Anaemia  iu  General, 35 

Varieties  of  Anaemia, 43 

Chlorosis,  Ancemia  of  Puberty, 47 

Anaemia  Lymphatica, 59 

Leucocythaemia, 75 

Anaemia  Splenica, 102 

Pernicious  Anaemia, 1 14 

Secondary  Anaemia, 129 

Toxan^emia, 130 

Parasitic  Anarmia, 132 

Index, 135 

vii 


ANAEMIA. 


INTRODUCTION. 

The  blood  holds  in  solution  certain  albumin- 
ous bodies,  of  which  the  principal  are  serum- 
albumin,  serum-globulin,  and  fibrinogen,  and  a 
number  of  mineral  substances,  the  chief  of 
which  are  common  salt  (sodium  chloride)  and 
sodium  carbonate.  These  may  be  classed  as 
the  invisible  constituents  of  the  blood,  and  their 
investigation  belongs  to  the  domain  of  the 
physiological  chemist.  In  addition,  it  holds  in 
suspension  certain  bodies,  the  red  and  white 
corpuscles,  which  are  open  to  direct  inspection, 
and  may,  therefore,  be  classed  as  the  visible 
constituents  of  the  blood.  The  study  of  these 
latter,  as  regards  their  form,  color,  size,  number 
and  relative  proportion,  is  the  province  of  the 
histologist,  and  it  is  with  these  properties  that 
we  are  concerned  in  this  treatise. 

The  red  corpuscles  of  man  are  circular  disks, 
with  rounded  edges  and  depressed  centres.  On 
account  of  the  difference  in  thickness  between 

A  1 


the  central  and  peripheral  parts  of  a  red  cor- 
puscle, it  is  impossible  that  its  entire  surface 
can  be  accurately  focused  by  the  microscope 
at  the  same  time,  and,  accordingly,  when  its 
centre  appears  bright  its  periphery  is  dark,  and 
vice  versa.  The  diameter  of  the  human  red 
corpuscle  is  about  j|g  of  a  millimetre,  or  -g^aVo  ot 
an  inch.  The  chemistry  of  the  red  corpuscles 
is  quite  complex,  and,  in  some  respects,  still 
unsettled.  The  most  important  ingredient, 
haemoglobin,  is  conspicuous  by  its  brilliant  op- 
tical properties,  and  its  amount  may  be  most 
readily  determined  by  these  alone.  It  is  the 
only  proteid  of  the  body  that  contains  iron,  and 
the  amount  of  this  mineral  in  the  ash  of  the 
blood  affords  a  method  of  determining  the 
amount  of  haemoglobin  in  a  given  specimen. 
It  is  by  means  of  the  hsemoglobin  in  the  red 
corpuscles  that  the  blood  conveys  oxygen  to 
the  tissues.  Haemoglobin  is  characterized  by 
the  readiness  with  which  it  absorbs  and  parts 
with  oxygen.  It  exists  in  the  blood  in  two.  dis- 
tinct forms  :  in  the  arterial  blood  as  oxy-haemo- 
globin,  and  in  the  venous  blood  as  reduced 
haemoglobin.  These  two  forms  are  readily 
distinguished  by  means  of  the  spectroscope. 


Haemoglobin  is  crystallizable,  the  crystals  being 
obtained  with  greater  or  less  ease  from  the  blood 
of  different  animals.  They  may  be  obtained 
most  readily  from  the  blood  of  the  rat,  by  simply 
mixing  it  with  distilled  water  on  a  glass  slide. 
Other  means  employed  with  the  blood  of  other 
animals  are  :  alternate  freezing  and  thawing  of 
the  blood,  the  passage  through  it  of  electric 
shocks,  of  the  vapors  of  ether  and  chloroform, 
and  the  addition  of  the  alkaline  salts  of  the  bile. 
The  largest  crystals  are  deposited  from  blood 
that  is  allowed  to  undergo  decomposition.  Thus 
obtained,  they  are  often  of  enormous  size — from 
three  to  five  centimetres  long.  This  is  explained 
by  the  supposition  that  putrefaction  destroys 
substances  which  are  preventive  of  crystalliza- 
tion. If  there  is  any  single  element  of  the  body 
that  deserves  to  be  called  "vital,"  it  is  undoubt- 
edly haemoglobin.  It  is  universally  present, 
and  conveys  to  the  tissues  the  element,  oxygen, 
that  is  most  essential  to  the  life  of  the  individual, 
while  its  diminution  below  the  normal,  even 
when  slight,  is  manifested  by  various  symptoms 
of  functional  disorder,  and  when  extreme  and 
long  continued,  leads  to  grave  and  irreparable 
organic  lesions.      Its   chemical  properties   are 


extraordinary,  and  apparently  contradictory. 
It  is  organic  and  yet  crystallizable  ;  it  has  an 
eager  affinity  for  oxygen,  and  yet  parts  with  it 
on  the  shghtest  demand ;  it  is  soluble  in  water, 
and  circulates  in  the  blood  without  leaving  the 
red  corpuscles ;  and,  finally,  without  losing  its 
identity,  it  exists  in  the  blood  in  two  distinct 
forms  :  in  the  arteries  as  oxy-hsemoglobin,  in 
the  veins  as  reduced  haemoglobin.  The  ab- 
sence of  this  substance  from  the  blood  in  greater 
or  less  degree,  is  at  the  root  of  the  various  forms 
of  anaemia,  about  to  be  considered. 

The  white,  or  colorless  corpuscles,  are  spher- 
ical masses  of  granular,  nucleated  protoplasm, 
having  a  diameter  of  io/-i^  or  23V0  o^  ^-^  inch. 
They  possess  the  power  of  spontaneous  move- 
ment, and  hence  are  sometimes  called  amoeboid 
cells,  from  their  resemblance,  in  this  respect,  to 
the  unicellular  rhizopod,  called  the  amoeba. 
They  exist  in  healthy  blood  in  about  the  pro- 
portion of  one  white  to  five  hundred  red  cor- 
puscles. Their  specific  gravity  is  less  than 
that  of  the  red  corpuscles,  and,  therefore,  if 
blood  be  placed  in  a  narrow  cylindrical  vessel 

*  T)ie  Greek  letter,  /i,  is  used  as  the  sign  of  the  micromilli- 
metre,  or  one-thousandth  of  a  milhmetre.  ^ 


and  kept  from  coagulating  by  a  temperature  a 
little  above  the  freezing  point,  or  by  the  addi- 
tion of  a  saline,  such  as  sodium  sulphate,  the 
red  corpuscles  will  collect  at  the  bottom  of  the 
vessel,  and  the  white  at  the  top.  Owing  to 
their  scanty  numbers,  great  difficulty  stands  in 
the  way  of  their  accurate  chemical  analysis. 
Nevertheless,  some  work  has  been  accom- 
plished in  this  direction.  Their  contractile 
power  is  probably  dependent  upon  a  substance 
closely  resembling  the  myosin  of  voluntary 
muscle.  Their  nuclei  may  be  isolated  from 
the  surrounding  protoplasm  by  the  action  of 
gastric  juice,  which  dissolves  the  protoplasm 
and  leaves  the  nucleus  intact.  The  latter  is 
composed  of  a  mucin-like  substance,  contain- 
ing phosphorus,  called  nuclein.  The  minute 
granules  scattered  throughout  the  substance  of 
the  white  corpuscles  are,  some  of  them,  soluble 
in  ether  and  alcohol,  and  therefore  regarded  as 
fat  granules ;  the  nature  of  the  granules  not 
thus  dissolved  is  unknown.  Glycogen  is  also 
contained  in  the  white  corpuscles,  as  may  be 
demonstrated  by  treating  them  with  a  solu- 
tion of  one  part  iodine,  and  two  parts  potas- 
sium iodide,  in  one  hundred  parts  water. 


6 

Besides  the  red  and  white  corpuscles,  other 
morphological  elements  exist  in  the  blood,  con- 
cerning the  character  and  function  of  which 
there  exists  considerable  confusion.  They  are 
the  haematoblasts  of  Hayem,  identical  with  the 
blood-plates  (Blutplattchen)  of  Bizzozero,  the 
microcytes,  and  the  advanced  lymph  disk  or 
invisible  corpuscle  of  Norris.  When  blood  is 
examined  under  the  microscope,  there  may  be 
occasionally  observed,  and  sometimes  in  large 
numbers,  certain  granular-looking  masses  of 
irregular  shape,  the  size  of  which  is  variable, 
but  may  considerably  exceed  that  of  the  white 
corpuscles.  They  are  known  as  Schultze's 
granule  masses.  With  strong  lenses,  it  is 
readily  seen  that  they  are  not  granular  or 
amorphous — like  the  amorphous  urates  seen  in 
urine — but  are  composed  of  distinct  and  inde- 
pendent individual  elements,"'^  which  latter  are 
the  haematoblasts  or  blood-plates.  "  They  are 
the  elementary  corpuscles  of  Zimmermann,  the 
globulins  of  Donne,  the  grai7is  sarcodiques  of 
Vulpian,  and  the  granulations  litres  of  Ran- 
vier.  The  latter  regarded  them  as  particles  of 
fibrin,  which  serve  as  centres   of  coagulation, 

*  This  was  first  demonstrated  by  Osier. 


just  as  a  cr}'stal  of  sodium  sulphate  dropped 
into  a  solution  of  the  same  will  serve  as  a 
centre  of  crystallization."  * 

These  bodies  are  not,  as  has  been  supposed, 
disintegration  products  of  the  white  corpuscles, 
for  they  may  be  seen  circulating  in  the  blood 
of  transparent  tissues,  such  as  the  mesentery. 
Their  function  is  intimately  concerned  with  the 
production  of  fibrin. 

The  microcytes  are  round  or  disk-shaped 
bodies,  much  smaller  than  the  red  corpuscles. 
They  vary  considerably  in  size,  their  average 
diameter  being  3/-^.  They  resemble  minute  red 
corpuscles,  and  sometimes  contain  considerable 
coloring  matter.  They  are  very  numerous  in 
idiopathic,  so-called  pernicious,  anaemia,  while, 
on  the  other  hand,  the  granule  masses  are  but 
scantily  present  in  that  disease.  Microcytes 
are  also  to  be  found  in  perfectly  healthy  blood. 

The  colorless  corpuscle  of  Norris  is  a  red  cor- 
puscle minus  its  coloring  matter.  Norris  claims 
that  it  is  a  young  red  disk  that  has  been  elabo- 
rated in  the  lymph  glands,  and  has  entered  the 
blood  by  the  thoracic  duct,  and  that  it  gradu- 

*The  Coagulation  of  the  Blood.     F.  P.  Henry,  Archives  of 
Medicine,  December,  1884. 


8 

ally  acquires  all  the  properties  of  a  mature  red 
corpuscle.  His  opponents  contend  that  it  is  a 
red  corpuscle  deprived  of  its  coloring  matter  by 
the  veiy  manipulations  used  to  demonstrate  it. 
The  question  is  still  unsettled. 

The  functional  power  of  the  blood  is  depend- 
ent upon  the  number  and  quality  of  its  red 
corpuscles.  When  a  deficiency  exists  in  either 
of  these  respects,  the  tissues  suffer  for  the  want 
of  oxygen — the  most  important  nutritive  ele- 
ment of  the  body.  When  the  degree  of  anaemia 
is  slight,  it  may  be  manifested  by  symptoms 
which  are  not  to  be  distinguished  from  neuras- 
thenia in  its  various  forms,  except  by  an  exami- 
nation of  the  blood.  The  latter  affection  often 
co-exists  with  a  perfectly  normal  condition  of 
the  blood.  When  the  anaemia  is  of  higher 
grade,  the  want  of  oxygen — equivalent  to  want 
of  breath — may  not  be  experienced  except  upon 
exertion,  of  which  the  amount  necessary  to  pro- 
duce this  symptom  is  in  inverse  ratio  to  the 
degree  of  anaemia.  In  extreme  cases,  simply 
raising  the  head  from  the  recumbent  position 
will  suffice  to  induce  breathlessness  or  even 
syncope.  Even  in  such  extreme  cases,  the 
symptoms  alone  will  not  suffice  for  diagnosis, 


for  there  are  diseases  of  which  the  most  promi- 
nent symptoms  are  due  to  irregular  distribution 
of  the  blood,  a  hyperaemia  of  one  vascular  dis- 
trict necessarily  causing  a  correlative  ansemia 
of  another,  while  the  constitution  of  the  blood 
is  normal.  The  most  conspicuous  example  of 
this  condition  is  furnished  by  Addison's  disease, 
in  which,  owing  to  vasomotor  paralysis,  there 
is  great  accumulation  of  blood  in  the  ab- 
dominal vessels  and  a  correlative  anaemia  of 
the  brain.  Here,  also,  dyspnoea  arises  upon 
slight  exertion ;  the  muscles  are  weak  and 
easily  fatigued,  and  in  extreme  cases,  during 
the  frequent  exacerbations  of  the  disease,  simply 
raising  the  head  from  the  pillow  is  sufficient  to 
induce  syncope.  Until  very  recent  times,  these 
symptoms  of  Addison's  disease  were  ascribed 
by  the  most  eminent  authorities  to  a  high  degree 
of  anemia.  It  is  now  established  that  in  such 
cases  the  constitution  of  the  blood  may  be 
normal,  and  that  the  symptoms  are  due  to  its 
irregular  distribution.  Further  instances  are 
unnecessary  to  prove  the  diagnostic  importance 
of  a  proper  examination  of  the  blood.  The 
presence  of  anemia  may  be  guessed  at  without 
such  examination,   and   the  diagnosis  (?)   con- 


10 

firmed  or  rejected  by  the  result  of  the  treatment, 
while  the  patient,  in  the  meantime,  may  have 
been  losing  what  might  have  been  saved  by 
proper  methods.  Not  only  the  bare  presence 
of  ansemia,  but  its  variety  and  degree,  are  to  be 
ascertained  by  examining  the  blood,  as  well  as 
its  progress  under  different  modes  of  treatment. 
In  short,  no  contribution  to  the  clinical  history 
of  a  case  of  anaemia  deserves  to  be  compared 
with  that  derived  from  an  examination  of  the 
blood. 

METHODS   OF   EXAMINATION. 

These  consist  in  the  enumeration  of  the  red 
and  white  corpuscles,  and  the  determination 
of  the  percentage  of  haemoglobin  in  the  former. 
The  instruments  used  for  counting  the  corpus- 
cles are  all  constructed  upon  the  same  principle, 
the  different  modifications  being  such  as  are 
designed  to  facilitate  the  rapid  counting  of  the 
cells,  and  the  easy  reckoning  of  their  percentage 
as  compared  with  the  standard  of  health.  A 
known  quantity  of  blood  is  diluted  with  a  known 
quantity  of  fluid,  and  in  a  cell  of  certain  depth 
and  superficies — the  latter  indicated  by  squares 
of  a  certain  size  ruled  upon  an  ocular  micro- 
meter, or  on  the  bottom  of  the  cell  containing  the 


11 

blood — the  number  of  corpuscles  is  counted. 
With  these  factors — the  depth  of  the  cell,  its 
superficies,  and  the  degree  of  the  dilution — the 
number  of  corpuscles  in  a  cubic  millimetre  of 
blood,  for  instance,  is  readily  estimated.  It 
is  self  evident  that  the  more  the  blood  is 
diluted,  the  easier  is  the  counting  of  the 
corpuscles,  and  the  longer  the  subsequent 
calculation.  The  chief  instruments  in  use 
for  counting  the  blood  corpuscles  are  the 
compte-globules  of  M,  Malassez,  for  a  de- 
scription of  which  see  Coniptes  Rendus  de 
L! Academie  des  Scietices,  Dec,  1872,  also 
These  de  Paris,  1873;  the  hematim^tre  of 
MM.  Hayem  and  Nachet,  described  in  the 
Coniptes  Rendus  de  L' Acadeinie  des  Sciences, 
26  Avril,  1875 ;  ^^i^  the  haemacytometer  of 
Dr.  Gowers,  of  London. 

The  different  instruments  for  counting  the 
blood  corpuscles  may  be  used  in  combination. 
Thus,  in  many  of  my  own  observations,  I  have 
used  Gowers'  pipettes  with  Hayem  and  Nachet's 
cell  and  eye-piece.  Thoma  and  Zeiss  {Her- 
inann's  Hand  duck  der  Physiologie,  IV,  Bd.  I), 
also,  have  constructed  an  apparatus  composed 
of  the  pipette  used  with  Malassez'  instrument. 


12 

known  as  the  mixer  [melangew')  of  Potain,  and 
a  cell  similar  to  that  of  Gowers.  The  instru- 
ments of  Gowers  and  Zeiss  are  superior  to  the 
others  mentioned,  in  that  they  may  be  used 
with  any  microscope  without  adjustment  for  the 
different  objectives  employed.  The  counting  is, 
however,  sometimes  rendered  very  difficult  with 
Gowers'  instrument,  on  account  of  the  large 
size  of  the  squares — ^^  of  a  millimetre.  The 
squares  in  the  cell  of  Zeiss'  instrument  are  only 
2V  of  a  millimetre,  rendering  the  counting  a  very 
easy  task.  Until  quite  recent  times,  it  was  sup- 
posed that  the  quality  of  the  blood  could  be 
accurately  determined  by  counting  its  corpus- 
cles. If  these  were  found  below  the  standard — 
5,000,000  per  cubic  millimetre — anaemia  was 
supposed  to  exist ;  while,  on  the  other  hand,  if 
above  this  standard,  anaemia  was  confidently 
declared  to  be  absent.  It  was  apparently  taken 
for  granted  that  the  red  blood  corpuscle  was  a 
constant  quantity,  a  unit,  containing  invariably 
the  same  amount  of  haemoglobin.  It  is  now 
thoroughly  established  that  the  amount  of 
haemoglobin  in  two  red  corpuscles,  from  differ- 
ent individuals,  may  vary  as  much  as  50  per 
cent.,  so  that  the  mere  number  of  the  corpuscles 


13 

does  not  afford  an  infallible  proof  of  the  pres- 
ence or  absence  of  anaemia.  When  the  cor- 
puscles are  decidedly  below  the  normal  average, 
anaemia,  of  course,  can  be  determined  by  a 
mere  count,  but  even  here  its  degree  can 
only  be  accurately  estimated  by  determining 
the  percentage  of  hsemoglobin,  the  reduction 
of  which  is  usually  greater  than  that  of  the 
number  of  the  corpuscles.  It  is,  however,  in 
those  cases  of  anaemia  in  which  the  number 
of  the  corpuscles  is  normal,  or  even  gi'eater 
than  normal,  that  the  superiority  of  the  haemo- 
globin test  is  unmistakably  manifested.  The 
writer  agrees  with  Hayem,  that,  if  one  had  to 
choose,  in  cases  of  this  sort,  between  the  two 
methods,  the  color  test  would  undoubtedly  be 
preferred.^ 

The  principal  point  to  be  determined  in  an 
examination  of  the  blood  is  the  functional  value 
of  the  red  blood  corpuscles,  which  bears  a  direct 
ratio  to  the  amount  of  haemoglobin   in  each. 

*  "  Si  dans  les  cas  de  ce genre,  cas  d'ailleurs  extremement  com- 
muns,  on  voulait  s'en  tenir  si  I'une  des  deux  methodes  d'examen 
du  sang,  c'est  done  sans  hesitation  au  precede  chromometrique 
qu'il  faudrait  donner  la  preference."  Recherches  sur  r anat. 
norm,  et path,  du  sang.     Paris,  1878. 


14 

As  a  rule,  when  the  number  of  blood  corpuscles 
is  normal,  the  amount  of  haemoglobin  is  also 
normal,  or  nearly  so,  but,  and  this  fact  deter- 
mines the  value  of  a  color  test,  there  are  numer- 
ous exceptions  to  this  rule.  Thus,  Baxter  and 
Willcocks  found  6,600,000  corpuscles  per  cubic 
miUimetre,  in  a  case  of  typhoid  fever,  but  they 
contained  only  45  per  cent,  of  the  normal  quan- 
tity of  haemoglobin,  making  their  functional 
value  equal  to  that  of  2,970,000  normal  corpus- 
cles ;  so  that,  in  spite  of  the  high  figures,  the 
degree  of  anaemia  was  great. 

Instruments  for  estimating  the  percentage  of 
haemoglobin  have  been  devised  by  Hayem, 
Malassez  and  Gowers,  of  which  the  most  simple 
is  the  globinometer  of  Dr.  Gowers.  I  have  used 
this  apparatus  with  much  satisfaction.  It  is 
light,  compact,  and  easily  manipulated.  The 
words  of  its  inventor  are  equally  applicable  to 
the  instruments  of  Hayem  and  Malassez.  "  The 
instrument  is  only  expected  to  yield  approxi- 
mate results,  accurate  within  two  or  three  per 
cent.  It  has,  however,  been  found  of  much 
utility  in  clinical  observations." 

From  these  introductory^  remarks,  the  import- 
ance, for  clinical  purposes,  of  a  proper  exami- 


15 

nation  of  the  blood  is  manifest.  It  is  a  signifi- 
cant fact  that  those  who,  in  the  course  of  their 
practice,  make  frequent  examinations  of  the 
blood,  encounter  cases  of  disease  never  met 
with  by  others,  with  perhaps  much  greater  op- 
portunities for  observation  ;  but  no  more  so  than 
that  the  oculist  has  become  able,  by  improved 
clinical  methods,  to  classify  cases  formerly 
vaguely  known  as  "amaurosis,"  into  retinitis, 
choroiditis,  atrophy  of  optic  nerve,  separation  of 
retina,  glaucoma,  etc.  The  wonderful  progress 
of  ophthalmology  in  recent  times  has  been  due 
to  the  skillful  handling  of  a  small  mirror,  and 
what  we  know  of  blood  diseases,  is  due  to  the 
microscope  in  conjunction  with  an  apparatus 
which  is  already  regarded  as  one  of  its  import- 
ant "accessories."  We  now  proceed  to  the 
consideration  of  our  proper  subject,  Anaemia. 

ANEMIA   IN   GENERAL. 

The  term  anaemia,  signifying  an  impoverished 
state  of  the  blood,  is  to  be  preferred,  both  on 
the  grounds  of  etymology  and  euphony,  to  such 
terms  as  spansemia,  oligaemia,  oligocythaemia, 
which  have  been  introduced  at  various  times 
on  the  plea  of  greater  accuracy.  It  has,  be- 
sides, the  great  advantage   of   possessing  its 


16 

exact  equivalent  in  the  French  and  German 
languages — "  anemie  "  and  "  andmier  All  the 
different  varieties  of  anaemia  are  characterized 
by  a  diminution  of  the  number  or  value  of  the 
red  blood  corpuscles  ;  that  is  to  say,  of  the  nor- 
mal amount  of  haemoglobin.  From  a  clinical 
point  of  view,  this  is  the  primary  and  essential 
morbid  condition.  It  is  supposed  and  argued 
that  this  reduction  in  the  amount  of  haemogrlo- 
bin  is  preceded  by  a  reduction  in  the  amount 
of  the  plasmatic  albuminates  ;  but  this  question 
is  quite  as  obscure  as  that  concerning  the  pre- 
albuminuric  stage  of  Bright's  disease.  Anaemia 
is  not  a  neurosis  or  a  functional  disorder,  as  one 
might  suppose,  from  the  loose  manner  in  which 
the  term  is  occasionally  employed,  but  a  sys- 
temic condition  dependent  upon  a  lesion  which 
can  be  demonstrated  with  the  utmost  precision. 
There  are  certain  predispositions  to  anaemia 
dependent  upon  sex,  age  and  constitution.  The 
female  sex  is  more  prone  to  anaemia  than  the 
male  ;  and  peculiarly  so  during  the  pregnant 
condition,  in  which,  owing  to  the  great  demands 
upon  the  blood  for  the  nourishment  of  the  foetus, 
anaemia  is  the  rule.  On  the  other  hand,  the 
female  sex  is  more  tolerant  of  anaemia  than  the 


17 

male,  which  is  partly  due  to  the  fact  that  the  life 
of  females  is,  as  a  rule,  more  sedentary.  ]\Tany 
women  go  through  a  long  life  without  any  par- 
ticular ailment,  but  are  known  to  possess  what 
is  termed  a  delicate  constitution.  Being  for- 
tunately free  from  any  constitutional  vice,  no 
organic  disorder  develops  ;  nevertheless  they  are 
chronic  invalids.  They  are  usually  treated 
with  excessive  consideration  by  friends  and  rela- 
tives of  their  own  sex,  and  regarded  by  the 
average  practitioner  as  lucrative  humbugs.  The 
fact  is,  that  such  women  are  suffering — if  such  a 
term  may  be  applied  to  a  condition  which  brings 
with  it  so  great  freedom  from  responsibility — from 
a  light  grade  of  chronic  anaemia.  It  is  astonishing 
upon  what  a  small  amount  of  food  such  persons 
support  a  long  existence  ;  but  it  is  to  be  observed 
that  if  the  income  is  small  the  output  is  still 
smaller.  Many  such  persons  play  the  role  of 
amiable  drones  in  the  hive  of  busy  workers. 
They  do  not  repine  at  their  lot,  preferring  to 
bear  those  ills  they  have  rather  than  fly  to  others 
(the  responsibilities  of  health)  that  they  know 
not  of. 

The   predisposing  influence  of   age  is  most 
marked  during  youth  and  advanced  life.     The 
B 


18 

demands  of  growth  during  adolescence  render 
the  equilibrium  of  the  blood  peculiarly  unstable. 
This,  also,  is  more  marked  in  females,  in  whom 
the  evolution  of  the  sexual  system  is,  as  a  rule, 
attended  with  more  systemic  perturbation. 

Anaemia  should,  undoubtedly,  be  classed 
among  the  tissue  changes  known  to  the  histolo- 
gist  as  "senile;"  indeed,  there  is  excellent 
ground  for  believing  that  it  is  at  the  root  of 
those  which  are  most  suddenly  disastrous,  to 
wit,  the  degenerations  of  the  walls  of  small 
blood  vessels.  During  the  inevitable  period 
known  as  the  "  decline  of  life,"  the  system  is 
especially  intolerant  of  nutritive  losses.  The 
recuperative  power  of  the  blood  is  impaired. 
It  is  just  at  this  period,  also,  that  the  diseases 
attended  with  such  losses  are  most  prevalent ; 
among  which  are  to  be  reckoned  chronic 
catarrhs  of  mucous  surfaces,  such  as  the  pul- 
monary and  vesical ;  hemorrhoids,  ulcers,  etc. 

Anaemia  may  be  congenital.  In  1883,  while 
examining  the  blood  of  several  new-born  chil- 
dren-at  the  Maternity  Hospital,  I  encountered 
the  following  case  : — 

"  Case  3. — Mary   C ,  born    5.20  a.m., 

November  5th,     Count  made  2.30  p.m.,  Novem- 


19 

ber  6th.  Child  weighed  six  and  three-fourths 
pounds  at  birth  ;  labor  natural.  Number  of  red 
corpuscles  per  cubic  millimetre,  3,625,000;  pro- 
portion of  white  cells  to  red,  i  to  145.  This 
case  was  undoubtedly  one  of  congenital  anemia. 
The  child's  only  appearance  of  malnutrition 
was  a  shriveled  state  of  the  integuments  of  the 
feet,  and  a  less  rosy  color  of  the  skin  than  normal. 
For  anew-born  child,  it  was  decidedly  pale.  This 
shriveled  state  of  the  skin  emphatically  nega- 
tives the  idea  of  a  relative  ansemia  from  excess 
of  fluid.  The  blood  was  probably  deficient  in 
quantity  (oligaemia)  as  well  as  defective  in 
quality  (oligocythsemia).  There  was  also  a 
decided  increase  in  the  number  of  the  white 
cells.  Careful  inquiry  proved  that  there  had 
been  no  hemorrhage  from  the  cord.  As  pos- 
sibly bearing  upon  the  congenital  imperfection 
of' this  child,  I  may  mention  the  fact  that  the 
parents  were  themselves  immature — the  father 
being  seventeen,  and  the  mother  eighteen  years 
old."*  It  is  possible,  also,  that  the  case  may 
have  been  one  of  congenital  syphilis. 

*  See  paper  entitled  "A  Contribution  to  the  Study  of  Icterus 
Neonatorum,"  by  Frederick  P.  Henrj',  m.d.  Archives  of 
Medicine,  October,  1883. 


20 

The  third  cause,  above  mentioned,  as  predis- 
posing to  anaemia,  is  cotistitutio7i.  No  better 
proof  of  the  existence  of  such  a  tendency  can 
be  brought  forward  than  the  report  of  the  above 
case  of  congenital  ansemia.  An  extended  series 
of  examinations  would  probably  show  that  such 
congenital  deficiencies  in  the  composition  of 
the  blood  are  by  no  means  uncommon.  Cer- 
tainly, the  widest  differences  of  external  appear- 
ance are  presented  by  the  new-born,  from  the 
pale,  puny  sickling  of  five  or  six  pounds,  to 
the  rosy,  vigorous  child  weighing  from  ten  to 
twelve.  With  proper  care,  the  puny  child  may 
thrive  and  grow,  perhaps,  too  rapidly,  and  pre- 
sent every  appearance  of  health,  but  in  after 
life,  under  circumstances  to  which  its  more 
vigorous  contemporary  would  rise  superior,  the 
i?i7iate  tendency  to  anaemia  will  manifest  itself. 
Precisely  similar  facts  are  observed  with  refer- 
ence to  the  other  tissues  of  the  body.  One  in- 
dividual will  not  only  retain  his  weight,  but  grow 
fat  upon  a  diet  which  another  would  regard  as 
but  little  removed  from  starvation. 

EXCITING   CAUSES   OF   ANAEMIA. 

It  is  hard  to  draw  a  sharp  line  between  the 
predisposing  and  exciting  causes   of  anaemia. 


21 

To  the  writer  it  seems  proper  to  include  among 
the  latter  such  causes  as  are  equally  operative 
in  either  sex  and  at  all  periods  of  life ;  but  in 
such  a  division  no  allowance  is  made  for  the 
wide  differences. in  individual  power  of  resist- 
ance. 

A  cause  will  excite  anaemia  in  an  individual 
with  an  innate  tendency  to  the  disease  ;  while 
in  another,  devoid  of  such  tendency,  it  will  not 
do  so,  unless  long  continued  or  frequently  re- 
peated. In  the  former  the  cause  deserves  to  be 
called  exciting  ;  in  the  latter  its  action  is  more 
closely  allied  to  that  of  the  causes  called  predis- 
posing. Bearing  this  in  mind,  the  exciting 
causes  of  anaemia  include  hemorrhage  and 
other  pathological  discharges,  sexual  excess,  in- 
sufficiency of  food,  light  or  air  (bad  hygiene), 
the  depressing  emotions  of  grief  and  anxiety, 
fever,  and,  finally,  whatever  interferes  with  the 
digestion,  absorption  and  assimilation  of  food. 
It  is  not  pretended  that  this  list  is  complete,  for, 
as  Immermann  remarks,  "Nearly  every  mor- 
bid process,  when  it  occurs  in  a  severe  form,  is 
sooner  or  later  followed  by  anemia."  It  would 
be  tedious  to  enter  at  length  into  even  the  chief 
exciting  causes  of  anaemia  ;  but  two,  which  are 


22 

the  most  frequently  encountered  in  medical 
practice,  deserve  more  than  a  passing  notice. 
These  are  hemorrhage  and  fever.  Experiments 
of  Vierordt  upon  the  lower  animals — dog,  rabbit, 
guinea  pig — show  that  death  ensues  promptly, 
when,  after  bleeding,  the  red  corpuscles  are  re- 
duced about  fifty  per  cent.  Later  observations 
show  that  these  figures  are  not  applicable  to 
human  beings,  whose  powers  of  resisting  hem- 
orrhage are  very  much  greater.  For  example, 
Behier  (quoted  by  Laache)  reported  the  case  of 
a  woman  whose  blood,  after  a  metrorrhagia, 
contained  but  19  per  cent,  of  the  normal  num- 
ber of  red  corpuscles  ;  having,  theretofore,  suf- 
fered a  reduction  of  81  per  cent.  The  woman 
recovered  after  transfusion.  Laache  examined 
the  blood  of  five  previously  healthy  women 
who  had  suffered  from  profuse  hemorrhage,  and 
found  the  red  corpuscles  reduced  respectively 
37,  61,  62,  64  and  68  per  cent.  In  three  of  the 
cases  there  was  complete  restitutio  ad  vitegrum , 
without  transfusion  ;  in  one,  death  occurred  from 
an  intercurrent  disease,  septicaemia  ;  and  in  the 
remaining  case,  improvement  was  progressing 
at  the  time  of  the  report.  It  must  be  borne  in 
mind,  however,  that  the  result  of  a  blood  ex- 


2S 

amination  after  hemorrhage,  depends  upon  the 
time  at  which  such  examination  is  made.  It  is 
self-evident  that,  if  from  a  quantity  of  blood 
outside  the  body  three-fourths  be  removed,  and 
a  sample  of  the  remaining  fourth  be  examined, 
its  centesimal  composition  will  be  the  same  as 
that  of  a  sample  taken  from  the  whole  mass. 
So,  also,  if  the  blood  in  the  living  vessels  be  ex- 
amined immediately  after  a  profuse  hemorrhage, 
its  composition  will  closely  resemble  that  of  the 
entire  volume  of  blood  before  the  hemorrhage. 
It  will  not  be  identical  with  it,  however,  for  dur- 
ing the  progress  of  a  hemorrhage,  the  lymph, 
the  tissue  juices,  and  any  ingested  fluids,  are 
rapidly  taken  up  by  the  blood  vessels  to  re- 
store the  blood  volume ;  so  that,  as  Immermann 
remarks,  the  immediate  effect  of  a  profuse 
hemorrhage  is  a  "  complex  dyscrasia,  made  up 
of  hypalbuminosis,  leucocytosis  and  oligocy- 
thaemia."  It  is  no  doubt  true,  in  the  majority 
of  cases,  that  even  during  the  progress  of  a 
hemorrhage,  owing  to  the  diminished  vascular 
tension,  the  "  osmotic  current  of  tissue  juices  " 
is  strongly  directed  toward  the  blood  vessels  ; 
but  I  believe  there  are  cases  in  which,  on  ac- 
count of  the  shock  to  the  system  produced  by 


24 

the  sudden  escape  of  a  large  amount  of  blood, 
this  current  is  extremely  feeble,  or  even,  for  a 
time,  held  in  abeyance,  and  in  which,  therefore, 
an  examination  of  the  blood,  immediately  after 
hemorrhage,  will  show  little  or  no  difference  in 
its  cellular  composition.  The  following  is  a  case 
in  point : — 

On  June  6th,  1885, 1  examined  the  blood  of  a 
woman,  Mary  L.,  set.  thirty-two,  who,  during 
the  preceding  four  weeks,  had  suffered  from  con- 
stant metrorrhagia,  which,  on  two  occasions, 
had  been  quite  profuse.  I  only  succeeded  at 
last  in  stopping  the  hemorrhagia  by  the  intra- 
uterine application  of  Monsell's  solution.  On 
June  5th  there  was  still  some  slight  oozing, 
which  had  entirely  ceased  by  the  6th,  the  day 
on  which  the  examination  was  made.  Number 
of  red  corpuscles,  per  cubic  millimetre,  4,600,- 
000.  Proportion  of  white  cells  to  red,  i  to 
460. 

"  As  far  as  the  number  of  red  corpuscles  per 
cubic  millimetre  is  concerned  (I  quote  from  my 
note  book),  and  the  proportion  of  white  to  red, 
the  blood  may  be  considered  absolutely  normal, 
but  the  woman  is  greatly  prostrated,  with 
blanched  skin  and  mucous  membranes.     The 


25 

volume  of  her  blood  is  evidently  greatly  dimin- 
ished." 

As  studies  of  the  centesimal  cellular  compo- 
sition of  the  blood  after  hemorrhage,  Laache's 
cases  are  defective,  as  he  himself  admits,  on 
account  of  the  time  between  the  hemorrhage 
and  the  first  examinations.  These  were  made, 
respectively,  in  Case  I,  on  the  20th  day  after  the 
hemorrhage;  in  Case  II,  on  the  21st;  in  Case 
III,  on  the  6th;  and  in  Cases  IV  and  V,  on 
the  5th. 

The  ansemia  of  fever  offers  certain  peculi- 
arities, to  which  I  have  called  attention  in  an 
article  in  The  Polyclinic  for  September  15th, 
1885,  entitled  "The  Latent  Ansemia  of  Typhoid 
Fever."  These  are,  in  part,  dependent  upon 
the  loss  of  water  sustained  by  the  system  in  all 
febrile  affections,  and  particularly  in  typhoid, 
o\\ang  to  its  long  duration  and  intestinal  com- 
plications. In  t}'phoid  fever,  which  may  be 
taken  as  a  type,  notwithstanding  the  evidences 
of  an  impoverished  state  of  the  blood,  afforded 
by  the  profound  adynamia  and  the  muscular 
tremors,  an  examination  during  the  height  of 
the  disease  will  show,  at  least,  a  normal  number 
of  red  corpuscles.     The  blood  taken  from  the 


26 

finger  is  of  a  dark  venous  hue,  does  not  flow 
readily  on  puncture,  and  is  evidently  inspis- 
sated. The  condition  is  precisely  the  reverse 
of  that  which  obtains  after  hemorrhage,  which 
is  a  point  of  some  interest,  since  it  has  been 
held,  by  at  least  one  eminent  authorit}%  that 
a  moderate  hemoiThage  during  the  course  of 
typhoid  fever  is  not  to  be  dreaded  as  a  compli- 
cation. This  clinical  fact,  if  it  be  one,  may  be 
explained  by  the  tendency  of  the  blood,  after 
hemorrhage,  to  regain  its  former  volume  by  the 
imbibition  of  water.  The  therapeutical  deduc- 
tion is  to  supply  fever  patients  abundantly  with 
water,  as  was  so  strongly  advocated  by  the  late 
Dr.  J.  Forsyth  Meigs. 

Although  the  number  of  red  corpuscles  in  a 
cubic  millimetre  of  blood  may  be  normal  in 
typhoid  fever,  their  value  is  decidedly  below 
par.  They  are  deficient  in  haemoglobin,  so 
much  so,  that  six  million  corpuscles  may  have 
only  the  functional  power  of  three  million. 

In  one  form  of  fever,  the  malarial,  recent  in- 
vestigations tend  to  show  that  a  micro-organism 
may  be  directly  active  in  destroying  the  red 
corpuscles.  These  organisms,  if  such  they  be, 
were  beautifully  demonstrated  by  Dr.  Council- 


27 

man,  of  Baltimore,  at  the  recent  meeting  of  the 
American  Association  of  Physicians.  They  oc- 
cupy the  interior  of  the  red  corpuscles,  and  are 
apparently  capable  of  distinct  amoeboid  move- 
ments. That  some  agency  destructive  of  the 
red  corpuscles  is  operative  in  certain  cases  of 
malarial  fever  is  proved  by  the  occurrence  of 
haemoglobinuria  as  a  symptom,  which  latter  is 
but  itself  the  sequence  of  a  preceding  hsemoglo- 
binaemia.  The  blood  corpuscles  are  destroyed 
while  circulating  in  the  vessels. 

SYMPTOMS   OF   AX.EMIA. 

It  is  customary'  for  medical  writers  to  describe 
the  immediate  effects  of  the  sudden  escape  of 
blood  from  the  vessels  as  typical  of  what  they 
call  acute  anaemia;  but  this,  in  my  opinion,  is 
a  mistake.  As  I  have  elsewhere  said:  "The 
symptoms  of  acute  loss  of  blood,  and  its  fre- 
quently fatal  termination  when  not  more  than 
one-half  the  normal  amount  has  been  lost,  are 
due  to  sudden  ischaemia  of  the  nerve  centres." 
Anaemia  undoubtedly  exists,  but  is  not  the  cause 
of  the  immediate  symptoms  of  hemorrhage. 
These  are  due  to  a  disorder  of  the  circulation, 
which  may  be  precisely  imitated  by  the  appli- 


28 

cation  of  Junod's  boot  to  one  of  the  lower  ex- 
tremities. 

The  remote  effects  of  a  hemorrhage,  that  is 
to  say,  the  condition  of  the  patient  when  the 
nervous  system  has  recovered  from  its  shock 
and  the  circulation  has  regained  its  equilibrium, 
may  be  taken  as  typical  of  acute  anaemia.  The 
chief  of  these  are  pallor  of  skin  and  mucous 
membranes,  muscular  weakness,  vertigo  or  syn- 
cope, on  exertion,  or  even  on  assuming  the  up- 
right position,  and  a  small,  soft,  frequent  and 
excitable  pulse.  In  addition,  there  is  thirst, 
anorexia,  or  an  appetite  that  is  irregular  and 
fanciful.  The  digestion  is  feeble  and  readily 
disordered.  There  is  a  prevailing  sense  of  cold, 
and  yet  on  slight  exertion  the  skin  becomes 
flushed  and  perspiration  breaks  out.  The  tem- 
per is  apt  to  be  peevish  and  irritable,  and  the 
normal  control  of  the  emotions  is  impaired. 
While  the  temperature,  upon  the  whole,  is  low- 
ered, irregular  pyrexia,  to  which  the  term  "  an- 
aemic fever"  has  been  applied,  is  commonly 
observed  in  the  severest  forms  of  anaemia.  The 
cause  of  this  fever  has  given  rise  to  much  dis- 
cussion, and  the  explanation  offered  by  Immer- 
mann   seems  to  be  the  most  plausible.     It  is 


29 

that,  owing  to  the  extreme  reduction  of  the  nu- 
tritive properties  of  the  blood,  the  tissues  suffer 
to  such  an  extent  as  actually  to  undergo  a  spon- 
taneous decay  or  necrobiosis,  which  is  attended 
with  the  evolution  of  heat,  as  is  always  the  case 
"when  chemical  compounds  of  a  more  stable 
kind  are  generated  from  such  as  are  less  stable," 
Hsemic,  systolic,  cardiac  murmurs,  and  a 
musical  murmur  (bruit  de  diable)  in  the  jugular 
veins,  are  among  the  physical  signs.  In  high 
degrees  of  anaemia  there  is  great  emaciation, 
which  is  generally  masked  by  oedema.  Hem- 
orrhages from  mucous  surfaces,  particularly  in 
the  form  of  epistaxis,  and  into  the  retina,  are 
of  common  occurrence,  A  fatal  termination  is 
generally  ushered  in  by  a  mild  form  of  delirium, 
which  may  be  for  days  preceded  by  a  condition 
of  lethargy,  from  which  the  patient  is  readily 
roused  to  full  consciousness,  but  relapses  into 
the  lethargic  state  as  soon  as  the  effort  to  attract 
his  attention  is  abandoned.  The  last  remarks 
are  only  applicable  to  certain  fatal  forms  of 
ansemia  into  which  there  is  reason  to  believe  an 
anaemia  simplex  may  sometimes  be  converted. 
If  an  anaemia  of  high  degree,  whether  it  origi- 
nate in  hemorrhage,  fever,  or  what  not,  becomes 


30 

chronic,  all  the  organs  of  the  body,  and  among 
them,  of  course,  those  concerned  in  blood  mak- 
ing, will  suffer  from  malnutrition,  so  that  a  con- 
dition which  was  at  first  what  is  termed  func- 
tional, may  eventually  become  organic  ;  that  is 
to  say,  dependent  upon  lesions  to  which  it  has 
itself  given  rise. 

ANATOMICAL  CHARACTERS. 

The  anatomical  characters  dependent  upon 
a  marked  and  long-continued  deficiency  of  red 
corpuscles,  are  dryness  and  translucency  of  the 
tissues  and  fatty  degeneration  of  the  heart,  in- 
tima  of  the  arteries,  renal  and  gastric  epithelia, 
and  the  hepatic  cells.  In  the  heart,  the  papillary 
muscles  are  chiefly  affected,  especially  those  of 
the  left  ventricle,  and  the  morbid  change  may 
be  detected  by  the  naked  eye  in  the  form  of 
minute,  yellowish  streaks,  which  have  been 
called  "tabby  mottling,"  or  " tabby-cat  stria- 
tion."  The  retinal  hemorrhages  are  dependent 
upon  degeneration  of  the  vessel  walls  and,  in 
one  form  of  anaemia,  upon  this,  in  connection 
with  a  plugging  of  the  vessel  affected,  with  white 
blood  corpuscles.  The  blood  is  seen  to  be  less 
than  normal  in  quantity  and  of  a  lighter  color 


31 

than  natural.  In  well-marked  cases,  it  is  of  a 
light  pink  color,  resembling  water  in  which  beef 
has  been  washed,  and  the  hue  which  it  imparts 
to  linen  is  sometimes  a  pale  yellowish  pink, 
which  would  hardly  be  recognized  as  a  blood 
stain.  Notwithstanding  the  deficiency  of  red 
corpuscles,  and  the  consequent  pale  tint  of  the 
blood,  the  muscles,  even  in  the  highest  degrees 
of  anaemia,  are  often  found  of  a  deep  red  color, 
and  the  adipose  tissue  of  a  rich  yellow. 

DIAGNOSIS. 

The  lighter  grades  of  ansemia  merge  imper- 
ceptibly into  health.  In  city  residents,  even  of 
the  well-to-do  classes,  whose  occupation  is  at- 
tended with  considerable  mental  work  and  its 
inevitable  anxiety,  anaemia  is  the  rule  rather 
than  the  exception.  A  number  of  corpuscles,  not 
below  5,000,000  per  cubic  millimetre,  of  which 
the  richness  in  haemoglobin,  as  determined  by 
Gowers'  haemoglobinometer,  does  not  fall  below 
90  per  cent.,  may  be  considered  normal.  This 
being  understood,  the  lightest  grade  of  anaemia 
would  be  expressed  by  the  following  formula : — 
N.  (number  of  red  corpuscles  per  cubic  m.)  =  100 
H.  (percentage  of  haemoglobin)  .  .  .  =.80 
V.  (value  of  each  corpuscle)    •     .     •     .     =  ^ 


32 

An  individual  whose  blood  condition  would 
be  expressed  by  these  figures,  might  show  little 
or  no  departure  from  health,  and  be  aware  of 
none.  I  have  several  times  found  such  figures 
in  young  men  whose  blood  I  have  examined 
for  the  purpose  of  comparing  one  counting  in- 
strument with  another.  In  the  above  example, 
N.  is  normal,  say  5,000,000,  but  these  5,000,000 
corpuscles  possess  only  four-fifths  the  normal 
percentage  of  haemoglobin,  and  are,  therefore, 
functionally  equal  to  4,000,000  normal  corpus- 
cles. 

Anaemia,  as  a  rule,  is  not  clinically  appreciable 
until  the  haemoglobin  represents  between  three 
and  four  million  corpuscles  per  cubic  m.  The 
actual  number  of  red  corpucles  may  be  five,  or 
even  six,  million  per  cubic  m.,  but  their  real 
value  is  sixty,  or  even  fifty,  per  cent,  of  the 
normal.  This  degree  of  anemia  is  attended  by 
both  signs  and  symptoms,  such  as  pallor,  a  ten- 
dency to  vertigo,  flushing  of  the  face,  perhaps 
tinnitus  aurium,  muscular  fatigue  on  slight 
exertion,  backache,  irregular  appetite,  and  a 
capricious,  captious  temper.  Such  a  condition 
might  be  merely  functional,  or  secondary  to  the 
early  stage  of  some  organic  affection,  such  as 


33 

Bright's  disease,  diabetes  mellitus,  carcinoma, 
phthisis,  etc. 

The  next  grade  of  anaemia  is  that  in  which 
the  real  value  of  the  corpuscles  is  between  two 
and  three  millions.  In  this  degree,  the  percent- 
age of  haemoglobin  may  be  much  greater  than 
in  the  preceding,  owing  to  the  fact  that  now  the 
corpuscles  are  decidedly  reduced  in  number. 
It  is  a  familiar  fact  to  all  students  of  blood 
diseases  that,  as  the  number  of  corpuscles  di- 
minishes, the  percentage  of  haemoglobin  in- 
creases, until  in  the  severest  forms  of  anaemia 
— those  termed  pernicious — it  may  equal  or  ex- 
ceed, even  double,  the  percentage  of  red  cor- 
puscles. A  reduction  of  both  number  and  value 
of  red  corpuscles  is  much  graver  than  a  mere 
diminution  of  value.  A  number  as  low  as 
3,000,000  generally  indicates  a  serious  state  of 
affairs,  and  may  depend  upon  a  more  advanced 
stage  of  one  of  the  diseases  above  mentioned, 
or  upon  one  or  other  of  the  diseases  of  the 
blood-making  organs,  to  be  considered  later. 

The  highest  grades  of  anaemia  are  those  in 

which  the  real  value  of  the  corpuscles  varies 

between    500,000  and  2,000,000  per  cubic  m. 

Such  figures  are   generally  the    expression  of 

c 


34 

diseases  of  the  blood-making  organs — spleen, 
lymph  glands,  bone  marrow — or  of  that  form 
of  '' ancematosis'"  to  which  the  term  pernicious 
has  been  justly  applied.  An  apparent  paradox 
is  met  with  in  these  intense  forms  of  anaemia, 
namely,  that  500,000  corpuscles  may  contain  as 
much  hsemoglobin  as  is  usually  found  in  one 
million.  When  this  is  the  case,  it  is  due  to  the 
fact  that  the  average  diameter  of  the  corpuscles 
is  decidedly  above  the  normal.  This  increase 
in  size  may  possibly  be  a  conservative  provision 
on  the  part  of  nature,  but  the  fact  remains  that 
increased  size  and  altered  shape  (poikilocytosis) 
of  the  red  corpuscles  must  be  regarded  as  of 
very  grave  significance.  An  average  diminu- 
tion in  the  size  of  the  corpuscles  is  generally 
combined  with  an  increase  in  their  number,  a 
set  of  conditions  commonly  observed  in  that 
form  of  anemia  called  chlorosis. 

PROGNOSIS. 

The  prognosis  of  anaemia  in  general  has  been 
sufficiently  hinted  at  in  the  preceding  remarks  ; 
but  it  may  be  well  to  emphasize  the  fact  that 
an  anaemia  per  se  is  never  grave  until  distinct 
anatomical  alterations  in  the  red  corpuscles — 


35 

alterations  of  size  and  shape — are  manifested. 
The  prognosis  of  secondary  ansemias  is  involved 
with  that  of  the  primary  disease. 

TREATMENT   OF  ANAEMIA   IN   GENERAL. 

On  account  of  the  general  prevalence  of 
Anaemia,  its  preventive  treatment  is  of  the 
utmost  importance.  The  great  majority  of  in- 
dividuals who  are  "run  down"  in  health,  or 
suffering  from  "nervous  exhaustion,"  which 
they  attribute  to  overwork,  are  simply,  as  before 
said,  more  or  less  anaemic.  Overwork  is  the 
unfortunate  scapegoat  whose  erratic  conduct 
renders  him  an  easy  prey  to  both  physician 
and  patient.  Work  may  be  rather  regarded  as 
a  raw,  nutritive  material,  which  is  usually  pre- 
pared and  served  in  an  underdone  condition. 
There  may  be  exceptional  cases  in  which 
anaemia  is  justly  attributed  to  overwork  alone, 
but  the  writer  has  never  seen  one.  There  is  a 
careless  way  of  regarding  this  matter  which 
leads  to  inaccurate  statements.  For  instance, 
if  the  hours  of  work  encroach  upon  those  of 
sleep,  it  is  the  want  of  sleep,  as  much  as  the 
excess  of  work,  that  is  to  blame  for  the  result- 
ing anaemia.     If  the  irrational  worker  neither 


36 

takes  the  time  to  eat  or  digest  his  meals,  his 
anaemia  is  due  to  inanition  or  indigestion.  If 
he  finds,  or  imagines,  that  the  steady  use  of 
tobacco,  coffee  and  alcohol  is  helpful  in  the 
kind  of  work  he  is  performing,  it  is  just  possible 
that  his  habits  are  alone  to  blame  for  his  im- 
paired physical  state. 

As  this  is  not  a  treatise  on  hygiene,  I  shall 
not  stop  to  indicate  the  amounts  of  food,  air, 
exercise  and  sleep  essential  to  preserve  the 
health  of  the  average  man,  woman  or  child ; 
but  I  cannot  refrain  from  pausing  to  condemn 
a  prevalent  error.  There  appears  to  be  a  wide- 
spread delusion  in  the  minds  of  young  men  that 
muscular  strength  and  bodily  health  are  synony- 
mous terms.  This  is  true,  indeed,  but  only  to 
the  extent  that  a  certain  a7nount  of  muscular 
strength  coincides  with  the  healthy  condition. 
There  is  a  limit  in  each  individual — a  Rubicon 
— the  ver}'  attempt  to  cross  which  is  attended 
with  danger.  The  story  of  the  man  who  began 
by  lifting  the  calf,  and  continuing  to  do  so  each 
day,  ended  by  lifting  the  cow,  is  one  of  those 
plausible  lies  which  only  serve  to  enhance  the 
beauty  of  truth  by  showing  how  a  germ  of  the 
latter  may  give  an  air  of  vraisemblance  to  a 


37 

tissue  of  falsehood.  It  is  a  pitiful  sight,  relieved 
only  by  its  absurdity,  that  of  a  young,  slender 
stripling  exhausting  himself  in  vain  efforts  to 
become  an  "athlete."  Out-door  sports  are 
excellent  for  the  growing  boy,  but  heavy  gym- 
nastics should  be  reserved,  as  a  rule,  for  those 
who  have  attained  their  full  growth.  The  boy 
will  defeat  his  object  of  becoming  a  strong  man 
by  practicing  them  too  early.  Let  him  possess 
his  soul  in  patience.  As  the  fisherman  says, 
in  La  Fontaine's  fable  : — 

"  Petit  poisson  deviendra  grand, 
Pour\'u  que  Dieu  lui  prete  vie." 

The  curative  treatment  of  a  case  of  anaemia 
is,  in  part,  determined  by  its  causes,  and  includes 
the  control  of  hemorrhage  and  other  patho- 
logical discharges  ;  the  removal  from  an  unfav- 
orable hygienic  environment;  the  administration 
of  a  proper  amount  of  nutritious  food,  and  the 
suppression  of  causes  which  interfere  with  its 
digestion  and  assimilation.  In  many  inveterate 
cases,  in  which  cure  is  still  possible,  this  result 
cannot  be  attained  without  weeks,  perhaps 
months,  of  persevering  treatment.  A  complete 
control  of  the  patient  is  essential,  and  to  this 


38 

end,  the  seclusion  insisted  upon  by  Dr.  Weir 
Mitchell  is  of  great  importance,  for  by  it  an 
important  obstacle  to  recovery  is  at  once  re- 
moved, to  wit,  the  demoralizing  sympathy  of 
injudicious  friends.  Excellent  results  have  been 
accomplished  by  the  means  so  judiciously  em- 
ployed by  Dr.  Mitchell,  namely,  rest,  seclusion 
and  passive  exercise  in  combination  with  the 
diet  and  medication  adapted  to  the  peculiar 
exigencies  of  the  case.  This  method  of  cure 
has  been  elaborately  explained  by  Dr.  Mitchell 
in  his  well-known  work,  entitled,  "  Fat  and 
Blood,"  and  is  doubtless  familiar  to  the  medical 
men  of  this  country.  I  have  seen  a  number  of 
cases  of  chronic  anaemia  whose  treatment  by 
this  method  has  been  attended  with  the  happiest 
results.  I  have  also  seen  it  fail,  as  is  to  be  ex- 
pected where  everything  fails,  namely,  in  the 
secondary  anaemia  of  malignant  disease,  and 
also  in  certain  advanced  cases  of  pernicious 
angemia,  4n  which  there  were  marked  alterations 
in  the  size  and  shape  of  the  red  corpuscles,  as 
well  as  extreme  diminution  of  their  number. 

The  advantages  to  be  derived  from  a  thorough 
employment  of  the  so-called  rest  cure  are  with- 
in the  reach  of  few,  and  in  the  majority  of  cases 


39 

our  main  reliance  is  on  drugs.  The  chief  of 
these  are  iron,  arsenic,  the  mineral  acids  and 
cod-liver  oil,  Hayem  also  reports  the  success- 
ful employment  of  ferrocyanide  of  potassium 
in  cases  of  decided  ansemia.  The  preparations 
of  iron  are  so  numerous  that,  supposing  them 
to  be  of  equal  value,  one  might  well  be  at  a  loss 
to  select  from  among  them.  This,  however,  is 
by  no  means  the  case,  and  I  will,  therefore,  in- 
dicate those  which  I  consider  the  best.  In  pill 
form  nothing  has  given  me  more  satisfaction 
than  the  formula  of  Blaud  : — 

R .     Ferri  sulphatis, 

Potassii  carbonatis,       aa         gr.  iss.  M. 

SiG. — One,  or  more,  after  each  meal. 

To  obtain  the  best  effects  of  a  ferruginous 
preparation,  it  is  often  necessary  to  give  it  in 
large  doses,  and  the  above  is  no  exception  to 
this  rule.  It  may  be  pushed,  if  well  borne,  to 
the  extent  of  three  pills  thrice  daily.  The  lac- 
tate, the  pyrophosphate,  the  malate  and  Oue- 
venne's  powder,  are  all  excellent  preparations 
of  iron.  Strychnia,  quinia  and  arsenic  may  be 
advantageously  combined  with  the  iron.  The 
latter  preparation  is  best  given  in  the  form  of 


40 

Fowler's  solution.  In  addition  to  its  specific 
action  upon  the  skin,  arsenic  has  for  a  long 
time  been  recognized  as  possessing  a  general 
beneficial  action  in  certain  states  of  impaired 
nutrition,  which  had  caused  it  to  be  classed 
among  the  agents  known  as  "  eutrophic." 
There  is  no  doubt  that  much,  if  not  the  whole, 
of  this  favorable  effect  is  due  to  the  increased 
amount  of  haemoglobin  in  the  blood,  which 
results  from  its  administration.  Arsenic  is  spe- 
cially indicated  in  anaemias  of  malarial  origin, 
although  its  use  is  by  no  means  limited  to  these 
forms. 

The  treatment  of  secondary  anaemias  is 
largely  influenced  by  the  nature  of  the  primary 
affection.  As  a  general  rule,  arsenic  will  be 
found  of  service  in  those  forms  of  secondary 
anaemia  in  which  there  is  a  state  of  congestion 
or  catarrh  of  the  gastro-intestinal  mucous  mem- 
brane. Osier  reports  good  results  from  its  use 
in  the  anaemia  of  heart  disease,  the  "  cachexie 
cardiaque'"  of  French  writers.  In  the  causa- 
tion of  this  form  of  anaemia,  the  obstacle  to  ab- 
sorption presented  by  the  engorgement  of  the 
gastro-intestinal  veins  is  an  important  factor. 

In  cases  with  a  syphilitic  history,  the  mercuric 


41 

chloride  may  be  usefully  administered  with  iron, 
as  in  the  following  formula : — 

R.     Hydrarg.  chlorid.  corrosiv.,     gr.j 
Tinct.  ferri.  chlorid.,  ^ij 

Glycerin.,  ^  ss 

Aquae,  q.s.  ad.  ,§iij-  M. 

SiG. — One  drachm  after  each  meal.  The  dose 
may  be  gradually  increased  to  two  drachms  thrice 
daily. 

The  ferrocyanide  of  potassium  recommended 
by  Hayem  is  worthy  of  trial,  on  account  of  its 
endorsement  by  so  distinguished  an  authority 
on  the  physiology  and  pathology  of  the  blood. 
He  begins  by  giving  one  gramme  (about  gr.  xv) 
daily,  in  two  powders,  and  gradually  increases 
the  dose  until  six  grammes,  in  six  powders,  are 
given. 

Transfusion  is  a  measure  which  has  been  so 
often  adopted  as  a  dernie7'  ressort  that  it  has 
fallen  into  discredit.  If  any  benefit  is  to  be 
derived  from  transfusion,  it  is  certainly  not 
when  the  patient  is  moribund.  After  the  sud- 
den escape  of  a  large  amount  of  blood,  the 
natural  process  of  restoration  may  be  best  imi- 
tated by  the  injection  into  a  vein  of  a  normal 


42 

saline  solution  (0.6  per  cent.  NaCl.),  the 
amount  of  which  must  be  determined  by  the 
effects  upon  the  patient ;  or  the  following  for- 
mula of  Hayem  for  intra-venous  injection  in 
cholera,  may  be  employed : — 

R .     Distilled  water,  i  litre 

Sodium  chloride,  pure,  5  grammes 

Sodium  sulphate,  pure,         10  grammes.      M. 
SiG. — Filter  and  inject  slowly  at  a  temperature  of 
38°  C.  (100.4°  F.) 

When  the  object  of  transfusion  is  not  so 
much  to  overcome  the  effects  of  sudden  ischae- 
mia  of  the  nerve  centres  as  to  introduce  a  gradual 
improvement  in  the  patient's  nutrition,  defibrin- 
ated  blood  should  be  employed. 

It  has  been  pointed  out  that  when  the  respira- 
tion is  greatly  embarrassed,  the  injection  into 
the  vessels  of  an  additional  amount  of  reduced 
haemoglobin,  such  as  exists  in  venous  blood, 
may  only  make  matters  worse  by  adding  to  this 
embarrassment,  and  so  accelerate  a  fatal  end- 
ing. In  such  cases  the  blood  to  be  transfused 
should  be  taken  from  an  artery.  Quite  recent- 
ly the  injection  of  defibrinated  blood  into  the 
peritoneal   cavity  and  into    the    subcutaneous 


43 

connective  tissue  has  been  practiced  with  ap- 
parent benefit.  The  dangers  attendant  upon 
the  transfusion  of  heterogeneous  blood  are  well 
known.  It  should  never  be  used.  Milk  has 
been  transfused  successfully  in  a  few  rare  in- 
stances, but  for  this  purpose  is  greatly  inferior 
to  defibrinated  blood.  It  is  apt  to  occlude  the 
vessels,  many  of  its  globules  being  much  larger 
than  the  largest  white  corpuscles.  If  used,  it 
should  be  boiled,  in  order  to  destroy  the  bacteria 
which  are  almost  sure  to  be  present. 

VARIETIES   OF   AN.EMIA, 

Anaemias  are  properly  classified  with  refer- 
ence to  their  origin.  The  nutritive  fund  of  the 
blood  is  continually  drawn  upon  in  the  processes 
of  nutrition,  and  if  the  demands  are  inordinate, 
as  in  fever  and  hemorrhage,  the  resulting  anae- 
mia may  be  justly  ascribed  to  undue  waste. 
Under  this  head  a  large  number  of  anaemic 
conditions  might  be  grouped.  A  large  propor- 
tion of  the  remainder  might,  with  equal  pro- 
priety, be  attributed  to  inadequate  supply  of 
nutritive  materials,  due  either  to  absolute  want 
of  proper  food,  or  to  its  imperfect  digestion  and 
absorption.  There  would  still  remain  a  number 
of  cases  in  which  both  of  these^ausative  factors 


44 

are  so  intimately  combined  that  it  is  impossible 
to  decide  which  of  them  deserves  the  greater 
etiological  importance.  A  division  based  upon 
such  physiological  data  as  above  pointed  out, 
although  desirable,  is,  with  our  present  knowl- 
edge, altogether  inadequate.  Like  .so  many 
classifications  in  other  departments  of  medicine, 
it  is  not  ample  enough  to  cover  our  ignorance 
of  the  subject.  In  a  previous  contribution*  to 
the  literature  of  anaemia,  I  advocated  a  division 
of  its  different  forms  into  essential  and  symp- 
tomatic, and  gave  the  following  explanation  of 
my  reasons  for  so  doing : — 

"By  essential  anaemia,  I  mean  those  forms 
of  the  affection  that  are  associated  with  disease 
of  the  cytogenic  organs,  or  with  congenital  mal- 
formations of  the  vascular  system,  namely,  the 
lymphatic,  splenic  and  medullary  anaemiae,  and 
chlorosis;  and  by  symptomatic  anaemia,  those 
forms  of  the  disease  associated  with  affections 
of  non-C}^ogenic  organs  which  interfere  with 
nutrition,  such  as  febrile  anaemia,  the  anaemia 
of  phthisis,  cancer,  Bright's  disease,  the  anaemia 
of  heart  disease — cachexie  cardiaque  of  Andral 
— the  anaemia  of  lead  poisoning  and  of  inani- 

*  Carrwright,  Essaj^  1881. 


45 

tion.  Malarial  and  syphilitic  anaemia  occupy 
the  border  line  between  the  two  classes.  When 
recent  and  dependent  upon  an  acute  attack, 
they  may  come  under  the  head  of  febrile  anae- 
mia, but  when  chronic,  they  are  frequently 
essential,  the  one  generally  of  the  splenic,  the 
other  of  the  lymphatic,  variety.  These  afford 
intei"esting  examples  of  the  conversion  of  a 
symptomatic  into  an  essential  anaemia,  and  it 
is  held  by  the  writer  to  be  highly  probable 
that  they  are  not  the  only  instances  of  such 
conversion." 

The  time  that  has  passed  since  the  above 
paragraph  was  written  has  only  served  to 
strengthen  the  opinions  it  contains,  more  espe- 
cially that  concerning  the  conversion  of  one 
form  of  anaemia  into  another.  At  present, 
however,  I  prefer  the  terms  "primary"  and 
"secondary"  to  "essential"  and  "symptom- 
atic," because  they  are  more  widely  employed 
and  more  in  accord  with  our  general  medical 
nomenclature. 

In  addition,  I  am  in  favor  of  a  third  division, 
to  include  those  forms  of  ansemia  due  to  the 
destructive  effect  of  toxic  substances  upon  the 
blood  corpuscles,  and  would  suggest  for  them 
the  term  toxancE7nia. 


46 

Anaemias  of  parasitic  origin  are  so  important 
in  certain  countries  (and  perhaps  more  so  in 
our  own  than  we  suspect)  as  to  merit  separate 
classification. 

The  following  classification  is  offered,  in  the 
belief  that  it  is  one  under  which  all  the  different 
varieties  of  anaemia  may  be  appropriately 
grouped  : — 

I.    PRIMARY   AN.^MIAS. 

Chlorosis. 

Lymphatic  anaemia  (Hodgkin's  disease). 

Splenic  " 

Leucocythaemia. 

Pernicious  ansemia. 

II.    SECONDARY   ANEMIAS. 

Anaemia  of  fever. 

*'  hemorrhage. 

"  phthisis. 

"  heart  disease. 

"  cancer. 

"  syphilis,  etc. 

III.    TOXANiEMIAS. 

Ansemia  of  lead  poisoning  (saturnine  anaemia). 
"  arsenic     " 

"  arseniuretted  hydrogen  poisoning. 

"  phosphorus  poisoning. 

"  nitric  oxide         " 


47 


lA'.    PARASITIC    AN.^MIAS. 

Anaemia  caused  by  Anchylostomum  duodenale. 
''  "         Bilharzia  haematobia. 

"  *'         Filaria  sanguinis. 

"  "         Plasmodium  malarise. 

CHLOROSIS.      AN.EMIA   OF   PUBERTY. 

With  the  advent  of  puberty  comes  the  most 
sudden  and  imperative  demand  upon  the  blood 
that  is  encountered  during  the  normal  life  his- 
tory of  the  individual,  and  this  is  superadded 
to  the  continued  demands  of  growth,  which  is 
most  active  at  this  period.  It  is,  therefore,  not 
surprising  that  an  anaemic  condition  is  common 
at  this  time  of  life  ;  the  wonder  is  that  it  is  not 
the  rule.  The  developmental  impulse  of  pu- 
berty will  rouse  from  their  dormant  existence 
any  congenital  imperfections  of  the  blood  such 
as  were  described  in  an  early  part  of  this 
work. 

A  great  deal  of  confusion  surrounds  the  sub- 
ject of  chlorosis,  which  is  partly  due  to  the  fact 
that  statements  made  by  well-known  authorities 
in  times  when  the  blood  was  but  rarely  exam- 
ined, have  been  repeated  ever  since  by  writers 
upon  the  subject.     The  researches  of  Johann 


48 

Duncan,  in  1867,*  demonstrated  that  in  chlo- 
rosis the  red  corpuscles  may  be  normal  in  num- 
ber, while  their  value — the  quantity  of  haemo- 
globin they  carry  —  is  greatly  reduced.  In 
Duncan's  cases — three  in  number — the  percent- 
age of  haemoglobin  was  0.3.  0.31  and  0.37,  the 
normal  standard  being  i.  While  there  can  be 
no  question  of  the  originality  and  value  of 
Duncan's  demonstration  that  the  coloring  mat- 
ter of  the  red  corpuscles  may  be  reduced  with- 
out a  corresponding  diminution  of  their  number, 
I  am  convinced  that  such  a  condition  is  not  pe- 
culiar to  chlorosis  or  any  other  form  of  anaemia. 
In  fact,  in  one  of  the  cases  upon  which  his  cele- 
brated observations  were  made  there  is  room 
for  doubt  as  regards  the  diagnosis,  owing  to  the 
fact  that  the  patient  had  a  splenic  tumor. 

By  chemical  analysis  of  the  blood,  in  cases 
of  chlorosis,  a  condition  has  been  detected 
which  is  thought  by  some  to  be  pathognomonic. 
Becquerel  and  Rodier,  and  Ouinquaud  have 
found  a  normal  proportion  of  albuminates  in 
the  plasma  of  chlorotic  blood,  while  in  the  blood 
of  anaemia  in  general,  they  are  said  to  be  di- 

*  Sitzungsbericht    der   K.    Acad,  der   Wissensch.  in  Wien. 
B. Iv,  1867. 


49 

minished.  Indeed,  the  first  two  observers  have 
found  a  condition  of  hyperalbuminosis.  Im- 
mermann,  in  his  excellent  article  in  Ziemssen's 
Cyclopaedia,  adopts  this  as  the  distinguishing 
trait  of  chlorosis,  which  he  regards  as  an  affec- 
tion sui  generis,  and  deprecates  any  attempt  to 
"  merge  it  in  the  great  ocean  of  anaemia. "  He 
holds  that  the  blood  in  this  affection  is  deficient 
in  haemoglobin  alone  without  any  corresponding 
diminution  in  the  albuminates  of  the  plasma. 

Quincke,  in  view  of  the  discrepancies  between 
his  own  examinations  of  the  blood  in  cases  of 
chlorosis  and  those  of  Duncan,  concluded  that 
there  must  be  at  least  two  kinds  of  chlorosis — 
the  one  with  a  normal  number  of  corpuscles 
deficient  in  haemoglobin  ;  the  other  with  a  di- 
minished number  of  corpuscles,  which  may  be 
either  normal  or  deficient  with  regard  to  their 
haemoglobin.*  Laache  has  examined  the  blood 
of  cases  presenting  the  typical  picture  of  chlo- 
rosis, and  found  it  normal  in  every  respect.    He 

*  "  Es  muss  daher  verschiedene  Chlorose  geben,  die  eine  mit 
normaler  Zahl  aber  verringertem  Hb-gehalt,  die  andere  mit 
verminderung  der  Zahl  derselben  wobei  der  Hb-gehalt  des 
einzelnen  normal  oder  ebenfalls  vermindert  sein  kann." — Vir- 
chow's  Arch.,  1872,  B.  liv.,  p.  537. 

D 


50 

proposes  for  these  anomalous  cases  the  term, 
pseudochlorosis.  He  contends  that  they  are 
cases  of  chlorosis,  because  their  symptoms  are 
identical  with  that  affection,  and  quotes  with 
approval  the  following  sentence  from  the  thesis 
of  Moriez :  "L'hematologiste  diagnostiquera 
I'anemie  et  ne  pourra  pas  diagnostiquer  la 
chlorose ;  ceci  est  affaire  au  clinicien."  I  may 
say,  in  passing,  that  I  entirely  dissent  from  this 
view  of  the  subject.  Virchow  has  endeavored 
to  place  chlorosis  upon  a  distinct  anatomical 
basis  by  demonstrating,  in  fatal  cases,  an  im- 
perfect development  of  the  heart  and  blood 
vessels.  He  has  found  the  aorta  of  a  full-grown 
woman  so  small  as  barely  to  admit  the  little 
finger,  and  its  coats,  while  preserving  their  elas- 
ticity, were  much  thinner  than  normal.  In 
addition,  degenerative  changes  in  the  intima 
were  often  met  with.  With  this  diminished 
calibre  of  the  arterial  system,  the  heart  may  be 
either  normal  in  size,  subnormal,  or  hypertro- 
phied.  When  it  is  recalled  that  the  blood  vessels 
and  the  red  corpuscles  are  derived  from  the 
same  embryonic  layer — the  mesoblast — the 
bearing  upon  the  pathology  of  chlorosis  of  a 
congenital  hypoplasia   of  this   portion   of  the 


51 

skeleton  becomes  manifest.  Virchow's  doctrine 
has  not,  however,  met  with  general  acceptance. 
One  of  the  most  important  functions  of  the  ar- 
terial system  is  its  power  of  adaptation  to  varying 
volumes  of  blood,  and  in  chlorosis,  to  employ 
the  words  of  Coupland,  "no  proof  has  been 
given  that  the  diminution  in  size  of  the  vessels 
has  not  followed  upon  diminution  in  the  total 
quantity  of  blood."  With  reference  to  this 
subject,  Fagge  remarks  :  "I  believe  that  such 
affections  are  not  congenital,  but  due  to  endo- 
carditis occurring  in  childhood.  Thus  it  seems 
to  me  that  the  hypoplasia  of  the  aorta,  instead 
of  being  itself  a  primary  defect,  is  but  a  second- 
ary result  of  the  valvular  lesion.  I  am  not, 
therefore,  disposed  to  attach  much  value  to  Vir- 
chow's observations  as  they  stand  at  present." 

From  the  above  remarks,  an  idea  may  be 
obtained  of  the  obscurity  surrounding  the  sub- 
ject of  chlorosis  from  an  anatomical  and  chemi- 
cal standpoint.  The  same  is  true  with  regard 
to  its  clinical  history.  The  most  various  con- 
ditions of  different  organs  and  systems  have 
been  described  as  more  or  less  symptomatic 
of  this  affection.  The  heart  has  been  found 
abnormally  small  in  some  cases,  abnormally 


52 

large  in  others.  The  genital  system  is  some- 
times imperfectly  developed ;  at  others,  its  devel- 
opment exceeds  the  normal  limits.  Sometimes 
amenorrhoea  exists,  and  may  either  precede  or 
follow  the  anaemic  symptoms.  On  the  other 
hand,  a  chlorotic  menorrhagia  has  been  spoken 
of.  The  number  of  red  corpuscles  has  been 
found  normal  in  some  cases,  increased  or  dimin- 
ished in  others.  Immermann's  view  that  the 
blood  of  chlorosis  is  peculiar  in  that  it  is  only 
deficient  in  haemoglobin,  the  plasmatic  albu- 
minates being  undiminished,  is  not  generally 
accepted,  for  "it  has  not  been  proved,  except 
in  a  few  cases  of  pernicious  anaemia,  that  the 
serum  albuminates  are  diminished  in  other 
forms  of  idiopathic  anaemia  besides  chlorosis."* 
With  regard  to  Laache's  cases  of  pseudochlo- 
rosis,  there  can  be  no  doubt  that  the  symptoms 
were  due  to  irregular  distribution  of  the  blood, 
especially  to  the  supra-diaphragmatic  portion 
of  the  trunk.  A  blood  of  good  quality,  if  not 
properly  distributed,  may  give  rise  to  some  of 
the  gravest  symptoms  of  anaemia,  such  as  pallor, 
syncope,  cardiac  palpitation,  feeble  pulse,  etc. 

*  Coupland.     Gulstoniau    Lectures    on    Ansemia.     Lancet, 
April  i6th,  1881. 


53 

This  is  well  seen  in  certain  cases  of  Addison's 
disease. 

The  confusion  in  which  the  subject  of  chlo- 
rosis is  involved  is  due  to  the  persistence  in 
regarding  it  as  a  disease  sui  generis,  distinct 
from  all  other  forms  of  anaemia.  The  truth  of 
the  matter  appears  to  me  to  be  simply  this  :  At 
the  time  of  puberty  there  is  an  urgent  physio- 
logical demand  upon  the  blood,  which  is  com- 
plied with  by  vigorous  individuals  without  detri- 
ment to  the  organism.  The  ordeal  of  puberty 
is  safely  passed.  In  less  vigorous,  but  still 
sound,  healthy  organisms,  a  decided  degree  of 
anaemia,  one  calling  for  treatment,  declares 
itself  at  this  time.  Finally,  in  those  with  any 
congenital  tendency  to  anaemia,  whether  this 
may  have  been  due  to  general  malnutrition 
during  intra-uterine  life,  or  to  a  special  hypo- 
plasia of  the  vascular  system  (the  mesoblast), 
the  anemia  of  puberty  is  intense.  The  case  is 
a  typical  one  of  chlorosis. 

The  term  chlorosis  is  too  convenient  to  be 
readily  abandoned,  for  under  it  has  been,  and 
will  be,  included  many  sins  of  diagnosis.  This 
is  a  questionable  advantage,  and  the  term  should 
only  be  used  to  express  an  anaemia  occurring 


54 

at  the  age  of  puberty  and  in  the  great  majority 
of  cases,  in  the  female  sex. 

DIAGNOSIS. 

The  diagnosis  of  chlorosis  is  included  in  that 
of  anaemia  in  general.  There  is  nothing  special 
with  regard  to  the  blood  to  mark  it  as  a  distinct 
disorder.  In  mild  cases  there  may  be  a  normal 
number  of  blood  corpuscles,  and  a  reduction 
in  the  amount  of  haemoglobin  which  may  be 
but  60,  or  even  50,  per  cent,  of  the  normal.  In 
severe  cases  the  number  of  corpuscles  and  the 
percentage  of  haemoglobin  are  both  reduced. 
In  the  well-marked  case  of  a  young  lady  aet. 
17,  whose  blood  I  recently  examined,  I  found 
the  following  figures  : — 

No.  red  corpuscles  per  cubic  millimetre,   2,690,000. 
Color  (haemoglobin) 32  per  cent. 

The  percentage  of  red  corpuscles  (haemic 
unit),  as  compared  with  the  normal  (5,000,000), 
was  54,  so  that  the  value  of  each  corpuscle  was 
only  If  of  the  normal,  making  the  2,690,000 
corpuscles  found  equal  to  1,594,080  normal 
corpuscles. 

The  corpuscles  were  smaller  than  normal  and 
perfectly  circular  in  outline.     The  white  cells 


55 

were  not  increased.  With  reference  to  the 
mere  number  of  the  red  corpuscles  in  chlo- 
rosis, Hayem  gives  3,520,000  as  the  mean  of 
eighteen  counts  (about  70.4  per  cent.),  and 
Coupland  about  3,000,000,  or  60  per  cent,  as 
the  mean  in  seven  cases.  As  concerns  the  size 
and  shape  of  the  corpuscles,  there  are  different 
statements.  As  a  rule,  they  vary  considerably 
in  size,  but  the  average  is  below  the  normal. 
This  is  also  the  opinion  of  Hayem  and  Laache, 
while  Malassez  considers  the  average  size  of 
the  corpuscles  to  be  increased.  This  discrep- 
ancy may  be  due  to  the  fact  that  in  the  more 
intense  forms,  those  approaching  pernicious 
anaemia  in  their  symptoms,  there  is  a  greater 
number  of  large-sized  corpuscles.  In  perni- 
cious anaemia  the  average  size  of  the  corpus- 
cles is  decidedly  above  the  normal,  and  since 
this  fatal  affection  is  due,  in  my  opinion,  rather 
to  the  prolonged  operation  of  the  ordinary 
causes  of  anaemia  than  to  one  that  is  specific, 
it  is  evident  that  those  cases  of  chlorosis  which 
approach  the  border  line  will  show  a  greater 
number  of  large  corpuscles  than  those  further 
removed  from  it.  Chlorosis  is  to  be  distin- 
guished  from   Bright' s  disease,  especially  the 


66 

insidious  form  so  often  associated  with  con- 
tracted kidneys,  and  from  tlie  early  stage  of 
phthisis.  The  former  differential  diagnosis  is 
to  be  made  by  careful,  perhaps  repeated,  exam- 
inations of  the  urine ;  the  latter  by  means  of 
the  thermometer.  According  to  Peter,  the  sur- 
face temperature  of  the  superior  intercostal 
spaces  is  normal  or  subnormal  in  cases  of  chlo- 
rosis, and  the  same  on  both  sides  ;  whereas,  it 
is  elevated  on  both  sides,  with  a  difference  be- 
tween the  two,  in  latent  tuberculosis.  In  chlo- 
rosis, also,  the  phosphates  of  the  urine  are 
below  the  normal  figure,  while  in  early  phthisis 
phosphaturia  is  quite  common.  The  cardiac 
murmurs  in  chlorosis  should  not  be  too  hastily 
set  down  as  haemic.  An  interesting  case  in 
point  is  reported  by  Dr.  T.  K.  Chambers  ("  Re- 
newal of  Life  ") — that  of  an  unmarried  servant, 
aet.  25,  with  symptoms  of  anaemia  so  marked 
that  the  attempt  to  stand  upright  caused  faint- 
ness.  There  was  pain  in  the  cardiac  region  and 
a  loud  blowing  murmur  with  the  first  sound. 
"  This  blowing  murmur  was  very  audible  all 
over  the  cardiac  region  and  up  the  large  vessels 
into  the  neck,  but  loudest,  and  of  a  harsher 
character  than  elsewhere,  just  at  the  level  of 


57 

the  aortic  valves."  Under  the  use  of  Mist. 
Ferri  Comp.  all  the  anaemic  symptoms  disap- 
peared in  twenty-one  days,  although  the  "  car- 
diac murmur  remained  as  loud,  if  not  louder, 
and  was  equally  ringing-  in  its  tone  at  the  level 
of  the  aortic  valves."  There  had  been  no  his- 
tory of  acute  rheumatism,  and  Chambers  con- 
cluded— and  I  think  most  justly — that  the  car- 
diac lesion  was  one  of  arrest  of  development. 

PROGNOSIS. 

The  prognosis  of  recent,  uncomplicated  chlo- 
rosis is  good.  If  of  long  duration,  the  nutrition 
of  the  cytogenic  organs  may  have  suffered  to 
such  an  extent  that  they  are  incapable  of  re- 
suming their  normal  functional  activity.  The 
case  is  now  inveterate,  or  pernicious,  and  its 
progress  is,  as  a  rule,  from  bad  to  worse.  The 
blood  corpuscles  now  resemble  those  of  the 
amphibia  in  their  number,  their  size,  their  shape 
and  their  percentage  of  haemoglobin,  and  re- 
covery is  all  but  hopeless.  Intercurrent  febrile 
and  inflammatory  affections  are  more  than  usu- 
ally dangerous  in  cases  of  chlorosis.  The  com- 
plications to  be  dreaded  in  chlorosis  are  phthisis, 
gastric  ulcer,  endocarditis  and  chorea.  There 
also  seems  to  be  a  certain  causal  relationship 


58 

between  chlorosis  and  exophthalmic  goitre — 
Graves'  disease.  The  best  test  of  the  ultimate 
prognosis  is  the  immediate  effect  of  proper 
treatment,  the  response  to  which  in  chlorosis  is 
remarkably  prompt  and  decided. 

TREATMENT. 

For  the  treatment  of  uncomplicated  chlorosis, 
we  have  a  specific  in  the  preparations  of  iron. 
To  show  numerically  the  effect  of  this  drug, 
I  append  the  following  figures  from  a  case 
published  by  me  in  the  Cartwright  essay, 
1881:— 

April   23d,  No.  red  globules  per  c.  mm.,  1,870,000 
April  30th,  "  "  "  2,945,000 

May      7th,  "  "  "  3,905,000 

May    19th,  "  "  "  4,315,000 

June    i6th,  "  "  "  4,695,000 

"  This  case  affords  a  remarkable  instance  of 
the  effect  of  iron  in  the  treatment  of  certain 
forms  of  anaemia.  It  is  classified  under  the 
head  of  chlorosis,  on  account  of  the  menstrual 
troubles  to  which  the  patient  has  been  subject 
since  the  period  of  puberty,  the  habitual  delicacy 
of  her  constitution  depending,  so  far  as  can  be 
ascertained,  upon  a  chronic  deficiency  in  the 
blood-making  function ;  and,  finally,  on  account 


59 

of  the  h^mic  cardiac  murmurs,  which  gradu- 
ally disappeared  as  the  quality  of  the  blood 
improved."  The  preparations  used  were,  first, 
the  reduced  iron,  which  was  afterward  changed 
to  the  pyrophosphate.  Blaud's  pill,  the  proto- 
chloride  of  iron  in  pill  form  (Rabuteau's  pill), 
the  lactate  and  the  malate,may  all  be  employed. 
There  are  many  cases  in  which,  owing  to  digest- 
ive troubles,  iron  cannot  be  immediately  em- 
ployed. The  best  method  of  preparing  such 
patients  for  specific  treatment  with  iron  is  a 
more  or  less  systematic  employment  of  the  rest 
cure,  including  massage,  passive  exercise,  and 
a  carefully  regulated,  nutritious  diet.  Before 
administering  iron,  the  physician  must  be  satis- 
fied that  a  cardialgia,  if  present,  is  not  dependent 
upon  a  gastric  ulcer.  To  effect  a  cure,  iron  must 
sometimes  be  given  in  heroic  doses.  Valuable 
therapeutic  data  may  be  obtained  by  frequent 
examinations  of  the  blood  during  the  treatment 
of  a  case. 

ANiEMIA  LYMPHATICA. 

This  disease  is  almost  as  rich  in  synonyms 
as  in  symptoms.  In  addition  to  the  title  at  the 
head  of  this  section,  the  following  terms  are 
commonly  applied   to    it :   Adenia,  Pseudoleu- 


60 

ksemia,  Malignant  Lymphoma,  Lymphaden- 
oma,  Lymphosarcoma,  and  Hodgkin's  Disease. 
These  are  far  from  being  equally  appropriate ; 
but  something  can  be  urged  in  favor  of  each 
one  of  these  terms,  in  accordance  with  the  point 
of  view  of  him  who  applies  it.  Thus,  the  sur- 
geon, having  his  attention  directed  to  the  ex- 
ternal manifestations  of  the  disease,  will  natu- 
rally employ  one  of  the  titles  ending  in  otna, 
while  the  countrymen  of  Hodgkin  will  con- 
tinue to  make  use  of  the  one  which  associates 
with  the  disease  the  name  of  the  discoverer.  I 
have  already  written  upon  this  subject,  under 
the  title  "  Hodgkin's  Disease,"  with  the  explan- 
ation that  "the  perplexing  nomenclature  of  this 
affection  has  led  the  writer  to  adopt  the  term 
'  Hodgkin's  Disease,'  in  the  belief  that  it  is 
more  generally  understood  than  any  of  the 
other  terms  employed."  From  the  present 
standpoint,  that  of  anemia,  it  seems  to  me  that 
the  term  Anaemia  Lymphatica  is  to  be  pre- 
ferred. I  refer  those  who  may  be  interested  in 
investigating  the  claims  of  Hodgkin  to  the  dis- 
covery of  this  disease  to  the  Medico-  Chirurgical 
Transactions,  Vol.  xvii,  1832,  where  it  is  first 
clearly  described  from  a  clinical  point  of  view. 


61 

From  a  purely  anatomical  standpoint,  Malpighi 
deserves  the  honor  of  having  been  the  first  to 
call  attention  to  the  pathological  combination 
of  enlargement  of  the  splenic  corpuscles  which 
bear  his  name  with  general  hypertrophy  of  the 
lymphatic  glands.  This  is  proved  by  the  fol- 
lowing quotation,  which  was  brought  to  the 
notice  of  Dr.  Hodgkin  by  Mr.  G.  O.  Heming  : 
"  In  homine  difficilius  emergunt  (speaking  of 
the  granules  in  the  spleen),  si  tamen  ex  morbo 
universum  glandularum  genus  turgeat,  mani- 
festiores  redduntur,  aucta  ipsarum  magnitudine, 
ut  in  defuncta  puella  observavi,  in  qua  lien 
globulis  conspicuis  racematim  dispersis  totus 
scatebat." 

The  a?iatomical  features  of  anaemia  lym- 
phatica  are  hypertrophy,  more  or  less  general, 
of  the  lymphatic  glands  ;  hypertrophy  of  the 
spleen,  due  to  enlargement  of  its  Malpighian 
bodies  ;  the  development  of  adenoid  tissue  in 
various  parts  of  the  body  ;  a  high,  although 
usually  not  extreme,  degree  of  ansemia  ;  and 
the  absence  of  leucocythaemia.  It  usually  be- 
gins as  a  local,  glandular  swelling  upon  the 
surface  of  the  body,  which  may  remain  lim- 
ited  for  weeks   or   months   to   one   lymphatic 


62 

group.  We  are  ignorant  of  any  law  governing 
the  extension  of  the  glandular  enlargement. 
At  times  it  follows  the  course  of  the  lymph 
stream  ;  at  others,  beginning  in  the  neck,  axilla 
or  groin,  it  will  next  attack  glands  in  either  of 
these  situations  on  the  opposite  side.  The 
superficial  glands  are  usually  chiefly  involved, 
especially  those  of  the  neck  and  axilla,  but 
cases  have  been  observed  in  which  the  morbid 
process  has  been  limited  to  the  deep  lymphatics 
of  the  trunk.  In  a  case  reported  by  Osier 
{^Canada  Med.  and  Surg.  Journal,  Feb.,  1881) 
the  retro-peritoneal  glands  were  the  only  ones 
affected.  The  enlargement  is  not  inflamma- 
tory, neither  does  it  cause  inflammation  in  the 
surrounding  connective  tissue.  The  individual 
enlarged  glands  are,  therefore,  freely  movable 
upon  each  other,  and  not  united  into  a  dense 
mass,  as  in  scrofula.  Their  consistence  varies. 
They  may  be  soft,  almost  to  the  point  of  fluc- 
tuation, or  of  nearly  cartilaginous  hardness,  but 
no  division  of  the  disease  can  be  based  upon 
such  differences,  for  hard  and  soft  glands  may 
be  present  in  the  same  case  at  the  same  time. 
While  the  change's  characteristic  of  scrofula 
— chronic  inflammation,  suppuration  and  case- 


63 

ation — are  conspicuous  by  their  absence,  there 
is  no  positive  antagonism  between  "  lymphad- 
enoma "  and  scrofula,  and,  therefore,  such 
changes  are  now  and  then  encountered.  They 
may  be  excited  by  traumatism  of  the  super- 
ficial tumors.  On  section,  the  soft  glands  are 
gray  or  grayish  red,  and  yield  an  abundant 
turbid  juice,  while  the  hard  ones  are,  on  section, 
of  a  yellowish  white  color,  and  exude  a  thin, 
transparent  fluid.  Ecchymotic  spots  and  apo- 
plectic extravasations  may  be  present  in  both 
forms  of  tumor.  Under  the  microscope,  the 
difference  in  consistence  of  the  growths  is  found 
to  be  owing  to  the  degree  of  thickening  of  the 
glandular  reticulum  and  septa.  The  soft  tumors 
are  due  solely  to  numerical  increase  of  the 
cells,  which  differ,  for  the  most  part,  in  no 
respect  from  normal  lymph  cells,  although, 
here  and  there,  larger,  darkly  granular  cells, 
with  two  or  three  nuclei,  may  be  met  with, 
and  true  giant  cells,  with  ten  to  twenty  nuclei. 
The  hard  tumors  present  the  same  appearances, 
with  more  or  less  thickening  of  the  glandular 
connective  tissue. 

The   splenic  enlargement,  although   a   char- 
acteristic feature,  is  believed   to   be    generally 


64 

secondary  to  that  of  the  glands,  for  cases  have 
been  observed  in  which,  with  general  involve- 
ment of  the  latter  and  secondary  formations  of 
adenoid  tissue  in  other  organs,  the  spleen  re- 
mained normal.  The  enlargement  of  the 
spleen  is  mainly  due  to  an  hypertrophy  of  those 
masses  of  adenoid  tissue  which  so  closely  resem- 
ble the  lymphatic  glands — the  Malpighian  cor- 
puscles. The  spleen,  in  this  disease,  never 
attains  the  colossal  size  it  sometimes  reaches 
in  leucocythaemia,  its  long  diameter  rarely 
exceeding  ten  inches.  The  diameter  of  the 
hypertrophied  Malpighian  corpuscles  varies  from 
that  of  a  pin's  head  to  one  or  two  centimetres, 
and  their  white  or  yellowish  color,  like  that  of 
the  lymphatic  glands,  contrasted  with  the  dark 
red  color  of  the  pulp,  gives  to  the  cut  surface  a 
characteristic  variegated  appearance.  Adhe- 
sions of  the  capsule  of  the  spleen  to  neighbor- 
ing organs  are  commonly  met  with.  The  en- 
larged corpuscles  may  easily  be  mistaken  for 
tubercular  masses,  especially  as,  under  the 
microscope,  they  are  seen  to  contain  the  same 
elements,  namely,  small  round  cells,  more  or 
less  altered  in  appearance,  and  giant  cells  con- 
tained in  a  reticular  tissue.     The  arrangement 


65 

of  these  constituents,  however,  is,  according  to 
Langhans,  different  from  that  of  tubercle.  In 
the  tubercular  nodule  the  reticulum  is  in  the 
centre,  or  in  a  zone  between  the  periphery  and 
the  centre,  while  in  the  lymphadenoid  nodule 
the  reticulum  occupies  the  periphery,  the  cells 
the  centre. 

The  infective  nature  of  Ansemia  Lymphatica 
is  shown  by  the  development  of  adenoid  tissue 
in  organs  and  tissues  of  which  it  is  not  a  normal 
constituent,  such  as  the  liver,  kidneys,  lungs, 
heart,  testicles  and  digestive  tract ;  less  fre- 
quently the  bones,  skin  and  nerve  centres.  The 
metastatic  nodules  spring  from  the  connective 
tissue  of  the  organ  ;  in  the  lungs,  from  the 
peribronchial  connective  tissue  ;  in  the  liver, 
from  the  capsule  of  Glisson,  etc.  The  suppo- 
sition that  they  may  arise  from  the  endothelial 
cells  of  the  lymph  spaces  has  not.  yet  been 
established.  The  microscopic  structure  of  the 
nodules  has  been  most  carefully  studied  in  the 
liver,  and  their  origin  proved  to  be  in  the  inter- 
acinous  tissue,  by  the  fact  that  a  bile  duct 
usually  occupies  their  centre.  Dr.  Burdon- 
Sanderson,  having  observed  a  thickening  of 
the  walls  of  the  intra-lobular  capillaries  and  a 

E 


66 

vacuolated  condition  of  the  liver  cells,  thinks  it 
probable  that  the  growth  may  originate  in  the 
glandular  tissue.  Instead  of  nodules,  a  diffuse 
leucocytal  infiltration  of  the  inter-acinous  tissue, 
as  in  incipient  cirrhosis,  is  sometimes  observed. 
In  the  lungs,  the  nodular  deposits  have  been 
often  mistaken  for  tubercle.  They  invade  the 
organ  from  behind  forward,  starting  from  al- 
ready enlarged  lymphatic  glands.  In  the  kid- 
ney the  deposit  assumes  the  form  of  inter-tubular 
streaks.  On  the  serous  membranes  it  occurs 
in  the  form  of  flattened  patches,  which  may  be 
half  an  inch  in  diameter.  Under  the  influence 
of  this  disease  the  thymus  gland  may,  although 
almost  completely  atrophied,  resume  its  original 
shape  and  size.  The  follicles  at  the  base  of  the 
tongue,  the  tonsils  and  the  retro-nasal  adenoid 
tissue  ("  pharyngeal  tonsil  "),may  be  so  greatly 
enlarged  as  to  completely  occlude  the  posterior 
nares.  The  thickening  of  the  intestinal  walls 
from  new  formation  of  adenoid  tissue  may  be 
enormous,  but  it  has  never  been  known  to  cause 
stricture.  In  a  case  reported  by  Dr.  Murchison, 
the  walls  of  the  duodenum  were  from  one  to 
two  inches  thick,  and  yet  the  "  intestinal  mucous 
membrane  corresponding  to  the  morbid  deposit 


67 

was  not  ulcerated,  and  the  calibre  of  the  gut 
did  not  appear  materially  narrowed."  Various 
forms  of  paralysis  may  be  due  to  the  deposit 
having  its  seat  in  the  nerve  centres,  but  such 
cases  are  exceedingly  rare.  The  blood  is  dimin- 
ished in  quantity  and  of  poor  quality.  Macro- 
scopically,  it  is  light  colored,  thin  and  un- 
coagulated  in  the  heart  chambers,  'or,  if  coag- 
ula  are  present,  they  are  quite  small.  Careful 
counts  of  the  blood  corpuscles  have  proved  that 
the  diminution  in  their  number  is,  as  a  rule,  by  no 
means  so  great  as  that  observed  in  cases  of  per- 
nicious ansemia.  In  four  cases  carefully  studied 
by  Laache  the  greatest  reduction  in  the  number  of 
the  red  corpuscles  was  1,830,000  per  cubic  mil- 
limetre, the  count  having  been  made  eleven 
days  before  the  death  of  the  patient.  In  a  case 
of  my  own,  a  boy  of  five,  with  enormous  en- 
largement of  the  right  cervical  glands,  the  num- 
ber of  corpuscles  per  cubic  millimetre  was 
5,462,000,  while  the  hemoglobin  was  only  sixty 
per  cent,  of  the  normal ;  so  that  the  functional 
value  of  the  corpuscles  was  diminished  by  forty 
per  cent.  In  a  case  reported  by  Dr.  Richard 
Geigel  [Deutsches  Archiv  fur  Klinische  Medi- 
cin,  Bd.  37,  p.   59,  1885),  that  of  a  boy  twelve 


68 

years  old,  the  right  side  of  whose  neck  was  occu- 
pied by  a  glandular  tumor  as  large  as  a  child's 
head,  almost  daily  counts  of  the  blood  corpus- 
cles were  made  from  June  7th  to  July  23d.  The 
lowest  count  was  960,000,  on  July  12th.  The 
percentage  of  haemoglobin  was  never  estimated. 

Effusion  into  the  pleural  and  abdominal  cavi- 
ties is  oftei!  found,  and  may  be  due  to  the  irri- 
tation caused  by  growths  of  adenoid  tissue  upon 
these  membranes,  or  to  the  pressure  of  en- 
larged glands  upon  the  vena  azygos  and  the 
vena  portae.  Hydrops  lactea  may  be  caused 
by  the  pressure  of  enlarged  glands  upon  the 
thoracic  duct.  The  bone  marrow  is  very  rarely 
affected.  Birch-Hirschfeld  knew  of  but  one 
case  in  which  this  tissue  was  abnormal.  The 
bones  themselves,  especially  the  vertebrae, 
sternum  and  ribs,  may  be  eroded  by  the  pres- 
sure of  enlarged  glands. 

Nature  of  the  Disease. — This  is  best  under- 
stood by  comparing  it  with  another  disease, 
with  which,  but  for  an  examination  of  the 
blood,  it  would  certainly  be  confounded, 
namely,  leucocythsemia.  Langhans,  in  view  of 
the  fact  that  the  principal  distinction  between 
these  two  diseases  is  the  absence  in  the  former 


69 

of  an  increase  in  the  number  of  white  corpus- 
cles, has  suggested  their  classification  under 
one  head,  such  as  adenia  or  lymphadenoma, 
with  the  division  into  a  leukaemic  and  a  non- 
leukaemic  form.  Dr.  H.  C.  Wood  is  of  the 
opinion  that,  "  clinically,  the  so-called  true  and 
false  leukaemia  are  the  same,  save  only  in  the 
matter  of  the  white  blood  corpuscles."  This  is 
also  the  view  of  Dr.  Wm,  Pepper,  who  in- 
cludes under  the  term  ''  ancBmatosis  "  the  affec- 
tions which  I  have  grouped  under  the  head  of 
primary  anaemia,  with  the  exception  of  chlo- 
rosis. The  term  is  apt,  convenient  and  com- 
prehensive, but  has  not  been  widely  adopted. 
While  admitting  the  fundamental  relationship 
between  these  various  forms  of  anaemia,  I  think 
that  better  scientific  work  will  be  accomplished 
by  continuing  to  treat  them  as  separate  affec- 
tions, by  dwelling  upon  their  points  of  diverg- 
ence. In  fact,  the  tendency  of  late  has  been 
rather  to  separate  than  to  unite  anaemia  lym- 
phatica  and  leucocythaemia.  Dr.  Moxon  and 
others  hold  that  there  is  no  such  disease  as 
pure  lymphatic  leucocythaemia,  the  grounds  for 
which  will  be  stated  in  treating  of  leucocy- 
thaemia. 


70 

The  disease  may  be  defined  as  an  infective 
hyperplasia  of  the  lymphatic  tissue  of  the  body, 
with  progressive  anaemia. 

Symptoms. — These  are  due  to  the  pressure  of 
enlarged  glands  and  new  formations  of  adenoid 
tissue  in  the  most  various  situations,  causing 
stenosis  of  ducts,  blood  vessels,  air  passages, 
oesophagus,  etc.  ;  and  to  the  profound  disturb- 
ance of  nutrition  and  resulting  anasmia,  which 
set  in  sooner  or  later.  By  the  pressure  of  the 
enlarged  cervical  and  bronchial  glands  may  be 
caused  cough,  dyspnoea  and  difficult  deglutition, 
which  may  all  be  aggravated  by  the  simul- 
taneous enlargement  of  the  tonsils  and  retro- 
nasal adenoid  tissue.  The  cerebral  circula- 
tion may  also  be  disturbed  by  pressure  upon 
the  cervical  veins.  In  the  axilla,  enlarged 
glands  may  cause  brachial  neuralgia  and 
oedema,  and  enlarged  inguinal  glands  may 
give  rise  to  similar  disturbances  in  the  lower 
extremity.  Enlarged  portal  glands  may  give 
rise  to  ascites  and  jaundice.  Sensor)^  and  motor 
paralysis  may  be  caused  by  growths  in  the 
brain  and  spinal  cord.  Digestive  disturbances 
may  be  due  to  the  growth  of  adenoid  tissue  in 
various  portions  of  the  alimentary  canal.     As  a 


71 

rule,  the  glandular  enlargement  does  not  cause 
pain  and  is  not  tender,  or  very  slightly  so,  on 
pressure.  The  same  is  true  with  regard  to  the 
spleen,  but  occasionally  the  hypertrophy  of  this 
organ  gives  rise  to  a  sense  of  weight  and  drag- 
ging in  the  left  hypochondrium,  or  even  pain 
that  may  radiate  to  the  back  and  opposite  side. 
Pyrexia  is  frequent  during  the  course  of  the 
disease,  but  presents  nothing  characteristic, 
being  sometimes  continuous,  at  others  remit- 
tent or  irregularly  intermittent.  Murchison  and 
De  Renzi  have  each  observed  a  case  in  which 
the  glandular  enlargement,  instead  of  gradually 
increasing,  was  paroxysmal,  coinciding  with 
attacks  of  pyrexia  of  several  days'  duration. 
After  each  attack  the  enlargement  subsided, 
but  remained  greater  than  before.  On  the 
other  hand,  Laache  has  reported  a  case  in  which 
during  the  febrile  attacks  the  glands  diminished 
in  size.  He  suggests,  in  explanation,  that  a 
pyrogenic  material  may  be  absorbed  from  the 
glands.  In  the  great  majority  of  cases  no 
change  in  the  dimensions  of  the  enlarged 
glands  is  observed  during  the  attacks  of  fever. 
The  remaining  symptoms  are  those  of  steadily 
progressive   anaemia,  namely,  muscular  weak- 


72 

ness,  paleness  of  skin  and  visible  mucous  mem- 
branes, palpitation  of  the  heart  with  sometimes 
a  systolic  murmur,  frequent  pulse,  epistaxis, 
oedema,  and  serous  effusion  not  accounted  for 
by  mechanical  obstruction. 

Diagnosis. — This  presents  certain  difficulties 
when  the  enlargement  remains  for  a  long  time 
limited  to  one  glandular  group.  It  is  to  be 
distinguished  from  scrofula,  sarcoma  and  car- 
cinoma. Strumous  glandular  enlargement  is 
generally  associated  with  other  signs  of  scrofula, 
such  as  affections  of  the  bones,  joints,  skin  and 
mucous  membranes,  and  especially  with  the 
characteristic y««Vj-  of  the  strumous  diathesis. 
The  glands,  too,  are  usually  adherent  to  each 
other  and  to  the  skin,  and  the  morbid  process 
slowly  advances  to  an  unhealthy  suppuration. 
In  sarcoma,  also,  the  glands  are  adherent, 
whereas  the  tumor  of  anaemia  lymphatica  is  dis- 
tinguished by  the  free  mobility  of  the  enlarged 
glands  upon  each  other.  This  communicates 
an  unmistakable  sensation  on  palpation,  which 
Southey  has  aptly  compared  to  that  experienced 
in  handhng  a  number  of  balls  enclosed  in  a 
net.  Carcinoma  is  almost  always  secondary, 
and  extends  by  glandular  contiguity,  while,  as 


73 

already  remarked,  there  appears  to  be  no  law 
governing  the  direction  of  the  progress  of 
lymphadenoma.  Leucocythaemia  is  excluded 
by  a  microscopic  examination  of  the  blood. 

Prognosis. — The  prognosis  of  this  disease  is  not 
so  hopeless  as  might  be  inferred  from  the  term, 
"malignant  lymphoma,"  applied  to  it  by  Bill- 
roth. In  estimating  the  probable  course  of  a 
case,  and  its  duration,  the  most  important  factor 
is  the  stage  which  the  growth  has  reached.  If 
local,  a  cure  is  not  only  possible,  but  highly 
probable,  provided  the  tumor  is  situated  in  one 
of  the  superficial  lymphatic  groups  ;  that  is  to 
say,  within  the  province  of  surgery.  If  the 
affection  has  become  general,  the  prognosis  is 
unfavorable  ;  but  even  then,  individual  cases 
present  wide  differences  with  regard  to  the 
rapidity  of  their  downward  course,  depending 
chiefly  upon  the  amount  of  pyrexia  and  the 
degree  of  anaemia.  The  average  duration  of  the 
disease  is  about  two  years,  but  is  largely  influ- 
enced by  the  preceding  health  of  the  patient, 
being  shortest  in  those  of  delicate  constitution.  It 
has  been  observed  to  run  a  very  rapid  course 
after  parturition,  especially  when  this  had  been 
accompanied  with  considerable  hemorrhage. 


74 

Treatmetit. — An  early  diagnosis  is  the  most 
important  requisite  to  a  successful  treatment. 
In  most  of  the  cases  on  record  the  affection  has 
remained  limited  to  one  of  the  superficial 
lymphatic  groups  for  a  varying  period,  during 
which  the  propriety  of  extirpating  the  tumor 
should  be  considered.  By  this  means  the  dis- 
ease may  sometimes  be  cured  and  its  progress 
often  delayed.  The  enlarged  glands  must 
sometimes  be  removed  as  a  palliative  measure, 
when  they  threaten  to  destroy  life  by  impeding 
respiration  or  deglutition,  or  cause  intense  pain 
by  pressure  upon  nerves.  Friction  over  the  en- 
larged glands  has  been  said  to  cause  a  reduc- 
tion of  their  size,  and  the  same  result  has  been 
attributed  to  the  application  of  electricity.  The 
general  nutrition  of  the  body  should  be  main- 
tained, as  far  as  possible,  by  a  diet  as  generous 
as  the  digestive  system  can  dispose  of.  The 
anaemia  should  be  combated  with  iron  and 
arsenic,  and  the  latter  is  believed  to  exert  a 
specific  action  when  injected  into  the  morbid 
growths.  Warfwinge  reports  several  cases 
cured  by  the  intra-splenic  and  intra-glandular 
injection  of  Fowler's  solution.  He  injected  four 
drops  of  the  solution  thrice  daily,  and  observed 


75 

a  steady  reduction  of  the  size  of  the  tumors  and 
a  gradual  improvement  of  the  condition  of  the 
blood. 

LEUCOCYTH^MIA. 

The  consideration  of  this  disease  naturally 
follows  that  of  the  one  which  has  so  often  been 
mistaken  for  it.  From  the  point  of  view  that 
the  genuine  should  always  have  precedence 
over  the  spurious,  it  might  well  have  come  first 
in  order,  but  the  object  of  this  work,  as  its  name 
implies,  is  to  keep  prominently  in  view  the  anse- 
mia  common  to  the  various  disorders  of  which 
it  treats.  From  this  standpoint,  the  anaemia 
of  pseudo-leukaemia,  being  uncomplicated,  de- 
serves the  precedence. 

Nomenclature. — Of  the  two  names  of  this  dis- 
ease, leucocythsemia  (white-cell  blood)  and  leu- 
kaemia (white  blood),  the  former  is  certainly  the 
more  accurate  ;  for  the  latter  might  be  applied, 
with  equal  propriety,  to  the  appearance  of  the 
blood  after  a  meal  containing  an  abundance  of 
fat,  and  in  many  cases  the  blood  presents  to  the 
unaided  eye  no  deviation  from  the  normal  ap- 
pearance. Nevertheless,  the  term  leucocythae- 
mia  has  been  practically  rejected  by  German 
writers,  whose   important  contributions  to  our 


76 

knowledge  of  this  disease  entitle  their  prefer- 
ences— or  prejudices — to  respectful  considera- 
tion. I  shall,  therefore,  employ  both  terms 
interchangeably  in  the  course  of  this  article, 
giving  the  preference,  when  an  adjective  is 
needed,  to  that  derived  from  the  shorter  of  the 
two. 

Anatomical  Characters. — This  disease  is  pre- 
eminently one  to  which  the  term  organic  or 
structural  may  be  applied ;  for  it  cannot  be  said 
to  exist  until  a  striking  change  in  the  composi- 
tion of  the  blood  has  become  manifest.  The 
degree  of  this  change  —  the  increase  in  the 
number  of  the  white  cells — necessary  to  con- 
stitute the  disease,  is  not  agreed  upon  ;  and  this 
is  not  surprising,  since,  as  all  are  aware,  the 
number  of  these  bodies  in  healthy  blood  can 
only  be  approximately  stated.  In  health,  after 
meals,  the  number  of  leucocytes  in  the  blood  is 
increased,  and  this  increase  coincides  with  a 
congestion  and  tumefaction  of  the  spleen,  of 
which  the  elastic  capsule  is  specially  adapted  to 
these  periodic  changes  of  volume.  This  condi- 
tion of  physiological  increase  in  the  number  of 
the  white  cells  is  known  as  leiicocytosis,  and  the 
same  term  is  applied  to  the  undue  proportion  of 


77 

these  bodies  sometimes  observed  in  fevers  and 
during  pregnancy.  A  narrow  boundary  line 
between  leucocytosis  and  leucocythsemia  cannot 
Be  drawn.  They  are,  rather,  separated  by  a 
broad  strip  of  territory,  which  either  may  invade. 
During  the  progress  of  a  case  of  leucocythaemia 
that  may  eventually  end  in  death,  there  may 
be  periods  of  remission,  during  which  the  pro- 
portion of  white  cells  to  red  may  be  but  little 
removed  from  the  normal ;  and,  on  the  other 
hand,  a  state  of  the  blood  at  first  regarded  as  a 
mere  leucocytosis  may  gradually,  by  its  per- 
sistence and  further  progress,  convince  the  ob- 
server that  he  has  to  deal  with  a  genuine  leuco- 
cythaemia. The  tendency,  however,  is,  rather, 
to  regard  leucocytosis  as  leucocythaemia  than 
the  reverse. 

Three  forms  of  leucocythaemia  are  described 
— the  splenic,  lymphatic  and  medullary,  which 
are  secondary  to  changes  in  those  organs — the 
spleen,  lymph  glands  and  bone  marrow,  uni- 
versally accepted  as  hcBmatopoietic ,  or  blood 
making.  Cases  have  been  supposed  to  be  due 
to  lesions  of  other  organs,  such  as  the  thymus 
and  thyroid  bodies,  the  tonsils  and  intestinal 
glands,  but  these  were  mostly  reported  before 


78 

Neumann  had  directed  attention  to  the  marrow 
as  a  fons  et  origo  ?nali,  and  there  is  no  proof 
that  such  cases  were  not  of  the  medullary  or 
myelogenous  form.  As  the  affection  is  mostly 
one  of  adult  life — the  greatest  number  of  cases 
occurring  between  thirty  and  fifty  years  of  age 
— the  part  taken  in  its  production  by  a  foetal 
organ,  such  as  the  thymus,  is  highly  prob- 
lematical. 

The  first  stage  of  the  morbid  process  in  the 
spleen  is  a  hypersemia,  which  may  be  so  intense 
in  degree  and  so  rapid  in  development,  as  to 
cause  great  enlargement  of  the  organ  and  sen- 
sations of  discomfort,  weight,  and  even  pain,  in 
the  left  hypochondrium.  The  tissue  of  the  gland 
is  soft  and  its  surface  irregular,  the  depressions 
corresponding  to  the  insertions  of  the  fibrous 
trabeculae.  At  this  period  the  condition  differs 
only  in  its  degree  and  persistence  from  that 
which  normally  exists  during  digestion.  Soon, 
however,  the  enlargement  acquires  a  more  per- 
manent— a  structural — foundation,  from  numer- 
ical hypertrophy  of  the  cells  of  the  splenic 
pulp.  The  size  of  the  organ  increases,  and  may 
become  so  enormous  as  to  fill  the  space  between 
the  ribs  and  groin  on  the  left  side,  and  extend 


79 

beyond  the  umbilicus  on  the  right.  The  results 
of  inflammation  of  the  capsule  are  commonly 
apparent  in  the  form  of  thickenings,  opacities 
and  adhesions  to  neighboring  organs.  The 
gross  appearance  of  the  cut  surface  is  variable. 
Sometimes  it  differs  in  no  respect  from  that  of 
a  normal  spleen  ;  at  others,  all  traces  of  the 
Malpighian  bodies  ha,ve  disappeared ;  the  sec- 
tion is  smooth  and  firm,  closely  resembling  that 
of  the  liver.  In  the  pure  splenic  form  of  leu- 
cocythaemia  the  Malpighian  bodies,  while,  per- 
haps, plainly  evident,  are  not  enlarged.  They 
become  so  only  in  the  lymphatic  and  lieno- 
lymphatic  forms.  Hemorrhagic  infarctions  are 
often  observed. 

The  alterations  of  the  lymphatic  glands, 
like  those  of  the  spleen,  are  due  to  simple 
hyperplasia,  and  have  been  already  described 
in  the  section  on  anaemia  lymphatica.  In 
leucocythsemia  their  consistence  is  usually 
soft. 

The  changes  in  the  bone  marrow,  to  which 
attention  was  first  called  by  Neumann,  are  two- 
fold. In  the  first  form  it  is  of  grayish-yellow  or 
yellowish-green  color,  and  closely  resembles  a 
thick,  creamy  pus  ;  in  the  second,  more  or  less  of 


80 

red  is  mingled  with  the  gray  or  yellow,  until  in  the 
most  marked  degrees  of  this  variety  the  medulla 
may  be  of  the  color  of  raw  beef.  These  variations 
in  color  are  explained  by  Ponfick  as  being  due  to 
varying  densities  in  the  accumulations  of  white 
cells  and  corresponding  variations  in  the 
amount  of  blood  in  the  vessels.  The  leucocytes 
are  seen,  under  the  microscope,  to  be  embedded 
in  an  extremely  fine  reticular  tissue.  In  this 
altered  marrow  there  may  be  apoplectic  extrav- 
asations such  as  have  been  described  as  occurring 
in  the  spleen  and  lymph  glands.  The  bones, 
of  which  the  medulla  most  frequently  under- 
goes these  changes,  are  the  sternum,  ribs  and 
vertebrae. 

In  other  than  lymphatic  organs,  any  alter- 
ations are  due  to  the  altered  state  of  the  blood, 
and  consist  of  the  fatty  degenerations  common 
to  anaemia  in  general  and  of  infiltrations  and 
nodular  deposits  of  leucocytes.  The  infiltra- 
tions are  most  common  in  the  liver  and  kid- 
neys, causing  considerable  enlargement  of  these 
organs.  The  nodules  have  been  observed  both 
in  the  substance  of  organs  and  on  their  serous 
surfaces,  as  well  as  on  the  mucous  membranes 
of  the  air  passages  and  stomach.    The  peri- 


81 

toneum  may  be  covered  with  gray,  semi-trans- 
parent nodules  varying  in  size  from  a  pin's 
head  to  a  pea,  and  so  closely  resembling  miliary 
tubercle  in  their  gross  and  microscopic  appear- 
ances that  the  absence  of  the  bacillus  may  be 
the  only  differential  point.  The  minute  struc- 
ture of  the  nodules  of  this  "  leukaemic  peritonitis" 
may  also  resemble  that  of  alveolar  sarcoma,  as 
in  a  case  described  by  Laache. 

Cha7iges  in  the  Retina. — In  well-marked 
cases  of  leucocythaemia,  certain  retinal  lesions 
are  commonly  observed,  to  which  attention  was 
first  directed  by  R.  Liebreich  in  1861.  Being 
generally  situated  near  the  periphery  of  the 
fundus  oculi,  they  but  seldom  cause  any  visual 
disturbance,  and,  therefore,  their  frequency  can 
only  be  estimated  by  an  ophthalmoscopic  ex- 
amination of  all  cases.  The  eye-ground  is  of 
an  orange-yellow  hue,  its  veins  pale  and  wider 
than  normal,  and  traces  of  hemorrhage  are 
scattered  along  their  course.  Other  spots  are 
observed,  of  which  the  appearance  indicates 
a  more  compound  structure  than  that  of  mere 
hemorrhage.  They  have  a  whitish-yellow  cen- 
tre and  a  reddish  border  of  extravasated  blood, 
and  are  analogous  to  the  lymphoid  deposits 
F 


82 

in  other  tissues.  The  cause  of  these  retinal 
hemorrhages  is  twofold.  They  are  favored  by 
the  malnutrition  of  the  vessels  from  deficiency 
of  red  corpuscles,  and  excited  by  the  obstructions 
from  excess  of  the  white. 

Changes  in  the  Blood. — The  characteristic 
feature  of  leucocythaemia  is  an  absolute  in- 
crease in  the  number  of  white  blood  cells,  which 
in  extreme  degrees  of  the  disease  may  be 
even  greater  than  that  of  the  red.  This  alter- 
ation in  the  cellular  composition  of  the  blood 
may  alter  its  macroscopic  appearance  by 
causing  it  to  assume  a  pale-red,  grayish-red, 
or  chocolate  color  ("milchchocolade")  ;  but  it 
would  be  exceedingly  rash  to  predict  the  exist- 
ence of  leucocythaemia  from  a  gross  examina- 
tion of  a  specimen  of  blood.  Such  a  caution 
will  not  seem  unnecessary  to  those  who,  like 
myself,  have  seen  a  case  reported  as  leucocy- 
thaemia in  which  the  blood  was  never  examined 
at  all.  The  white  cells  are  by  no  means  uni- 
form in  size.  In  one  of  Hosier's  cases  the 
smallest  were  one-third  smaller  than  the  red  ; 
the  largest  four  times  larger  than  the  red.  It 
is  doubtful  whether,  as  Virchow  supposed,  any 
diagnostic  significance  can  be  attached  to  such 


83 

variations  ;  for  in  a  case  of  pure  splenic  leucocy- 
thsemia  the  leucocytes  have  varied  in  diameter 
from  5  jj.  to  15  a.  Virchow  holds  that  in  the 
latter  variety  the  leucocytes  in  the  blood  are 
identical  with  the  cells  of  the  splenic  pulp,  and 
that  in  the  lymphatic  form  they  are  uninucleated 
like  the  cells  of  the  lymphatic  glands.  Before 
attempting,  however,  to  make  the  diagnosis  of  a 
disease,  it  is  necessary'  to  establish  its  existence, 
and  that  of  the  so-called  lymphatic  leucocy- 
th^mia  is  emphatically  called  in  question.  In 
the  medullary  form,  Neumann  has  found  in  the 
blood,  red  nucleated  cells  such  as  normally  in- 
habit the  marrow,  and  regards  them  as  charac- 
teristic of  this  variety.  They  are  not  always 
present,  having  been  searched  for  in  vain  by 
Mosler  in  a  typical  case  of  medullary  leu- 
kaemia {Berl.  klin.  IVoch.,  1876,  No.  49). 

The  degree  of  ansmia  is  rarely  extreme, 
ases  may  steadily  proceed  to  a  fatal  termina- 
tion without  a  reduction  of  more  than  fifty  per 
cent,  of  the  normal  number  of  red  corpuscles, 
although  exceptional  cases  occur  in  which  the 
number  of  red  corpuscles  is  exceedingly  small ; 
for  example  ,0.5  million  per  cubic  millimetre. 
There  are  no  characteristic  changes  in  the  size 


84 

and  shape  of  the  red  corpuscles.  The  value  of 
the  latter  (their  percentage  of  haemoglobin)  is 
well  maintained,  rarely  sinking  below  seventy- 
five  per  cent.  A  point  of  some  importance 
with  reference  to  the  pathogeny  of  the  disease 
is  that  the  number  of  white  and  red  cells  to- 
gether is  less  than  that  of  the  normal  number  of 
red.  Certain  pointed  octahedral  crystals  were 
discovered  in  leucocythaemic  blood  by  Charcot 
in  1853,  identical  with  those  subsequently  ob- 
served by  Leyden,  in  1 871,  in  the  sputa  of 
asthmatics.  In  i860,  in  a  case  reported  by  Dr. 
Calvin  Ellis,  Dr.  White  found  "  numerous  mi- 
nute crystals.  They  were  colorless,  elongated, 
faintly  marked,  rhombic  octahedra,  exhibiting 
irregularities  of  form,  indicating  an  organic  na- 
ture." To  these  crystals  he  gave  the  name  of 
"  Leiikosi?ty  In  1863  Dr.  Howard  Damon  dis- 
covered, in  the  leucocythjemic  blood  of  a  boy, 
certain  crystals  which,  he  asserts,  "  differed  en- 
tirely, in  form,  size,  color,  degree  of  resistance 
at  atmospheric  influences,  refractive  and  other 
properties,  from  all  known  crystals  of  the  human 
blood.''  They  were  composed  of  "  hexagonal 
and  pentagonal  plates  of  unequal  sides,  of  rec- 
tangular plates   in   the   form    of    squares   and 


85 

parallelograms,  and  also  of  a  few  triangular 
plates.  Some  of  these  crystals  were  twice  the 
size  of  the  red  blood  corpuscles  in  the  same 
field  of  view."  The  name  of  '' Leiicocrystallin  " 
was  applied  to  them  by  Dr.  Damon.*  Certain 
normal  constituents  of  the  spleen  have  been 
found  in  leucocythaemic  blood,  such  as  lactic 
and  formic  acids,  leucine  and  hypoxanthine. 
The  specific  gravity  of  the  blood  is  diminished 
in  leucocythsemia  ow4ng  to  the  fact  that  the  red 
corpuscles  are  replaced  by  the  lighter  leuco- 
cytes ;  and,  further,  because  the  normal  propor- 
tion of  water  is  retained.  The  proportion  of 
fibrin  is,  as  a  rule,  increased. 

Clinical  History. — In  the  insidious  nature  of 
its  onset,  and  its  gradual  progress,  leucocy- 
thasmia  resembles  many  fatal  diseases  which  run 
a  chronic  course.  The  first  symptoms  com- 
plained of  are  those  of  anaemia  in  general,  such 
as  muscular  weakness,  lassitude,  indisposition 
to  exertion,  either  physical  or  mental,  anorexia, 
indigestion,  and  dyspnoea,  on  exertion.  As  the 
case  progresses,  other  symptoms  arise,  of  which 
some  are  to  be  attributed  to  leuksemic  deposit  in 

*  See  Bolyston  Prize  Essay  on  Leucocythsemia,  1864. 


86 

the  parts  affected.  Among  these  are  hemor- 
rhages, either  spontaneous  or  traumatic;  the 
former  variety  being  most  commonly  met  with 
in  the  form  of  epistaxis  ;  the  latter,  after  the  ex- 
traction of  teeth.  Diarrhoea  is  now  the  rule, 
and  oedema  of  feet  and  legs  and  ascites  finally 
set  in.  The  last-named  symptoms  are  most 
common  when  the  spleen  is  greatly  enlarged 
and  indurated,  and  are  favored  by  deposits  in 
the  liver  and  by  the  leukaemic  peritonitis  above 
mentioned.  Singular  anomalies  are  sometimes 
observed  in  the  course  of  this  disease.  For  ex- 
ample, although  the  appetite  is  generally  mark- 
edly deficient,  often  to  the  point  of  absolute 
anorexia,  it  may  be  voracious,  as  in  a  case 
obser\^ed  by  Prof.  Da  Costa  (Am.  Jour.  Med. 
Sci.,  Jan.  1875),  i^  which,  in  spite  of  an  inordi- 
nate consumption  of  food  and  the  absence  of 
diarrhoea,  the  loss  of  flesh  was  progressive.  On 
the  other  hand,  in  a  case  reported  by  Mosler,  in 
which  the  blood  was  chocolate-colored  and  the 
white  cells  were  to  the  red  as  two  to  three,  the 
digestion  was  unimpaired  and  the  body  weight 
maintained.  Dizziness,  aggravated  by  move- 
ment, may  be  a  marked  symptom.  In  the 
splenic    form,  sensations  of    weight,  dragging 


87 

and  pain  are  felt  in  the  left  hypochondrium  ;  and 
in  the  medullary  variety,  tenderness  of  bones, 
particularly  the  sternum,  may  be  detected. 
Visual  disturbances  may  be  due  to  hemorrhage, 
to  leuksemic  deposit,  or  to  leukaemic  retinitis  ; 
but  marked  retinal  changes  may  be  observed 
in  cases  which  have  presented  no  symptoms  of 
eye  disease.  There  is  no  peculiar  facies  of  this 
disease.  The  extremepallor  of  pernicious  ane- 
mia is  rarely  observed.  On  the  contrary,  the 
cheeks  often  present  a  circumscribed  flush, 
even  in  a  late  stage  of  the  affection.  There  is 
nothing  typical  in  either  pulse  or  respiration, 
but  fever  of  irregular  type  is  invariably  met  with 
at  some  period  of  the  clinical  history.  The 
proportion  of  white  cells  to  red  is  dim^inished  by 
the  occurrence  of  suppuration  in  any  part  of  the 
body.  When  the  leukaemic  cachexia  is  fairly 
established,  the  enlarged  spleen  may  diminish 
greatly  in  size  without  any  corresponding  im- 
provement in  the  symptoms.  In  a  case  reported 
by  Laache,  the  spleen,  which  had  projected  to 
the  right,  beyond  the  median  line  and  downward 
almost  to  the  symphysis  pubis^  gradually  con- 
tracted until,  just  before  death,  it  extended  but 
three  centimetres  below  the  left  costal  border. 


88 

Hypoxanthine  is  found  in  the  urine  as  well  as 
in  the  blood,  and  in  the  former  fluid  the  pro- 
portion of  uric  acid  is  increased,  sometimes  to 
six  or  eight  times  the  normal. 

A  division  of  the  course  of  the  disease  into 
two  stages  has  been  suggested :  the  first  con- 
sisting of  the  development  of  the  morbid  pro- 
cess in  the  haematopoietic  organ  or  organs  first 
attacked  and  in  the  blood ;  the  second,  of  the 
extension  of  the  process  to  other  non-lymphatic 
organs.  This  division,  although  excellent  from  an 
anatomical  standpoint,  is  too  objective  for  clinical 
purposes.  The  secondary  leukaemic  deposits  can- 
not be  detected,  as  a  rule,  in  any  organs  but  the 
lymph  glands,  assuming,  for  the  moment,  that 
the  enlargement  of  these  organs  is  secondary. 

Pathogenesis. — To  properly  appreciate  the 
cause  of  any  deviation  from  the  normal  com- 
position of  the  blood,  it  is  necessary  to  under- 
stand how  that  composition  is  produced  and 
maintained.  In  the  problem  before  us — the 
nature  of  leucocythsemia — the  first  step  is  to  de- 
cide whether  there  is  any  normal  relationship 
between  the  r^d  and  white  cells.  If  there  be 
any,  it  is  manifest  that  the  red,  on  account  of 
their  greater  functional  importance,  their  size, 


89 

shape,  color  and  number,  are  derived  from  the 
white,  and  not  the  white  from  the  red.  The 
question,  therefore,  is  one  concerning  the  origin 
of  the  red  corpuscles ;  and  those  who  have 
studied  it  will  doubtless  agree  with  me  that 
there  is  scarcely  a  subject  in  physiology  con- 
cerning which  our  notions  are  so  fragmentary 
and  confused.  This  being  the  case,  it  is  im- 
possible to  offer  more  than  an  hypothesis  of  the 
nature  of  leucocythasmia. 

All  authorities  are  agreed  that  in  adult  life 
the  lymphatic  system — in  which  are  included 
the  spleen,  lymphatic  glands,  and  red  marrow 
— is  the  sole  source  of  the  red  blood  corpuscles. 
The  cells  of  the  splenic  pulp,  the  smaller  uni- 
nuclear cells  of  the  lymphatic  ganglia,  and  the 
red,  nucleated  marrow-cells — first  described 
by  Prof.  Neumann,  of  Konigsberg,  in  1868, 
and  subsequently  called  by  Malassez,  "cellules 
hemoglobiques ' ' — are  by  some,  perhaps  different, 
means  converted  into  the  bi-concave  discs  of 
the  circulating  blood.  Time  is  requisite  for  this 
conversion — a  time  of  incubation  in  the  blood- 
making  organs.  Any  unusual  activity  of  the 
circulation  in  these  glands  may  hasten  the  exit 
of  their  cells,  and  cause  them  to  appear  in  the 


90 

blood  in  an  immature  condition.  This  is  demon- 
strated by  the  physiological  concurrence  of 
leucocytosis  with  splenic  post-prandial  conges- 
tion. In  leucocythsemia,  there  is  a  persistent 
hyperaemia  of  spleen  or  other  blood-making 
organ,  which  prevents  the  leucocytes  from  at- 
taining their  proper  development.  They  enter 
the  circulation  as  leucocytes.  This  view  is 
endorsed  by  Dr.  Richard  Norris,  of  Birming- 
ham, and  held  by  others,  who  do  not  agree 
with  him  concerning  the  stages  of  the  process 
by  which  the  white  cells  are  normally  elaborated 
into  red  corpuscles.  Norris  contends  that  in 
health  the  great  majority  of  the  leucocytes  in  the 
blood-making  organs  are,  before  entering  the 
circulation,  converted  into  a  pale,  colorless,  bi- 
concave disc,  which  he  terms  the  "  advanced 
lymph  disc."  This  corpuscle  acquires  haemo- 
globin, and  with  it  its  full  functional  perfection. 
The  white  blood  corpuscles  represent  those 
leucocytes  which  have  prematurely  entered  the 
circulation,  for  instance  after  a  meal.  These  lat- 
ter, however,  may  develop  into  red  corpuscles 
in  the  circulation.  The  former  mode  of  ori- 
gin of  red  corpuscles  Norris  calls  the  "  major 
process  "   of  blood-formation  ;    the    latter,  the 


91 

"minor  process,"  and,  therefore,  in  accordance 
with  his  views,  "  leuksemia,  in  a  word,  is  the 
encroachment  of  the  minor  upon  the  major 
process  of  blood-making." 

Several  observers  have  noticed  a  diminution 
or  absence  of  amoeboid  movement  in  the  white 
cells  of  leucocythaemic  blood.  "  The  earliest 
observations  on  this  point  were  made  by  Dr. 
Laking,  in  1873,  ^^^  remained  unpublished. 
The  results  were  communicated  by  Dr.  Pye- 
Smyth  to  the  Pathological  Society  in  1878,  and, 
in  the  same  year,  to  the  Lancet,  by  Dr.  Cafavy. 
Neumann  also,  in  1878,  found  amoeboid  move- 
ments wanting,  or  very  sluggish,  in  a  case  of 
leukaemia,  although  they  were  active  in  the 
corpuscles  of  fluid  from  blisters  in  the  same 
patient."  {Lancet,  1880,  ii,  769.)  Dr.  John 
Cafavy,  who  has  given  special  attention  to  this 
subject,  concludes  that  "  the  colorless  corpuscles 
in  leukaemia  are  dead,  or  dying,  and  hence 
incapable  of  development."  This  functional 
incapacity  of  the  white  cells  may  be  referred  to 
the  shortness  of  their  stay  in  the  lymphatic 
organs,  of  which  the  hyperaemia  prevents  their 
reaching  the  normal  term  of  their  gestation. 
They  are  to  be  regarded  as  abortive  products. 


92 

Under  this  section  it  is  appropriate  to  con- 
sider the  question,  which  has  been  raised,  as  to 
whether  the  customary  division  of  this  disease 
into  three  varieties,  the  splenic,  lymphatic  and 
medullary,  is  warranted.  A  primary  splenic 
leucocythaemia  being-  universally  accepted,  it 
remains  to  consider  whether  the  lymphatic 
glands  and  the  bone  marrow  may  be  the  start- 
ing point  of  the  disease.  Some  authorities, 
while  not  explicitly  rejecting  the  lymphatic  and 
medullary  varieties,  do  so  tacitly  by  describing 
no  other  than  the  splenic.  Dr.  Moxon  is  the 
most  outspoken  upholder  of  the  doctrine  that 
the  spleen  is  the  only  starting  point  of  leuco- 
cythaemia, and  emphatically  rejects  the  theory 
of  a  lymphatic  leuksemia,  which  he  stigma- 
tizes as  a  "myth."  He  holds  that  the  enor- 
mous accumulations  of  leucocytes  in  the  lymph 
glands  and  bone  marrow  are  secondary  de- 
posits from  the  blood,  and,  in  support  of  this 
view,  he  has  demonstrated  that  the  leucocytes 
normally  present  in  the  lymph  spaces — which 
have  been  shown  by  Dr.  Klein  to  be  out-wan- 
dered white  blood  cells — are  greatly  increased 
in  number  in  cases  of  leucocythaemia.  These 
cells   are    conducted    through   the    lymphatic 


93 

vessels  to  the  glands,  and  if  these  are  pervious, 
re-enter  the  blood  ;  if  not,  the  glands  enlarge 
by  the  continual  accession  of  out-wandered 
blood  cells  ;  "  so  that,"  Dr.  Moxon  concludes, 
"  lymphatic  leukaemia  is  a  myth  ;  and  the 
pathology  of  leukaemia,  now  so  complex,  should 
be  simplified,  when  it  will  better  conform  with 
the  clinical  uniformity  which  characterizes  the 
disease."  I  am  inclined  to  accept  Dr.  Moxon's 
opinion  in  so  far  as  the  lymphatic  variety  is 
concerned,  for  the  reason  that  in  anaemia  lym- 
phatica  we  find  a  lesion  of  the  glands  identical 
with  that  which  exists  in  lymphatic  leukaemia. 
The  last-named  affection,  assuming  its  existence 
for  the  sake  of  the  argument,  is  made  up  of 
lymphatic  anaemia  plus  leucocythcemia,  I  be- 
lieve, however,  that  there  is  substantial  proof 
of  the  existence  of  a  primary  medullary  leukae- 
mia. For  example,  in  a  case  observed  by  Vir- 
chow,  fracture  of  the  femur  appeared  to  be  the 
determining  cause.  In  another,  reported  by 
Mursick,  the  disease  attacked  a  soldier  five 
days  after  amputation  for  a  gunshot  wound  of 
the  knee-joint,  and  at  the  autopsy  osteo-myelitis 
of  the  femur  was  found.  The  patient  had  been 
previously  healthy.    In  the  remarkable  case  of  a 


94 

sea  captain,  reported  by  Mosler,  in  whom  the  dis- 
ease followed  prolonged  exposure  to  cold  during 
an  Arctic  winter,  pain  and  tenderness  over  the 
entire  length  of  the  sternum  were  among  the 
earliest  symptoms,  and  speedily  became  so  in- 
tense as  to  compel  the  man  to  desist  from  any 
kind  of  manual  work.  The  list  of  cases  such 
as  those  last  referred  to  is  so  long,  and  the 
cases  themselves  so  remarkable,  that  those 
who  are  at  all  familiar  with  them  feel  the  ne- 
cessity of  great  caution  in  discussing  the  ques- 
tion of  a  primar}'  medullary  leukaemia.  As 
above  stated,  I  believe  the  evidence  is  in  favor 
of  such  an  affection,  and,  with  the  object  of 
obtaining  further  confirmation,  I  would  suggest 
to  hospital  surgeons  and  their  assistants  the  im- 
portance of  examining  the  blood  after  injuries 
of  the  bones. 

JEtiology. — The  male  sex  is  more  predisposed 
to  this  disease  than  the  female,  the  male  cases 
on  record  standing  to  the  female  in  the  pro- 
portion of  about  two  to  one.  The  influence  of 
age  is  not  striking,  although  the  disease  occurs 
most  frequently  during  adult  life,  and  between 
the  ages  of  thirty  and  fifty.  Neither  infancy 
nor  old  age   is    exempt.     Cases  in   infants  of 


95 

fifteen  and  sixteen  months  have  been  reported 
by  Trousseau  and  Hosier,  and  one  of  Vidal's 
cases  was  sixty-nine  years  old.  Dr.  Goodhart 
has  also  reported  to  the  Clinical  Society  of  Lon- 
don six  cases  under  two  years  of  age.  Poverty 
includes,  in  one  word,  a  number  of  predisposing 
factors,  such  as  an  unfavorable  hygienic  en- 
vironment, insufficient  food,  and  the  depressing 
emotions  of  care  and  anxiety.  A  few  cases 
have  been  attributed  to  traumatism  of  the  spleen, 
and  others,  as  already  stated,  to  that  of  the 
bones.  There  can,  I  think,  be  no  doubt  that 
long-continued  exposure  to  severe  cold  has 
excited  the  disease  in  several  instances. 

Diagnosis. — This  can  be  made  in  no  other 
way  than  by  a  microscopic  examination  of  the 
blood,  and  to  warrant  the  diagnosis  of  leucocy- 
thsemia,  the  increase  in  the  number  of  the  white 
cells  must  be  absolute  as  well  as  relative.  In 
well-marked  cases  the  microscopic  inspection 
of  a  drop  of  blood  will  suffice  for  the  barest  pur- 
poses of  diagnosis,  but  will  give  no  idea  of  the 
grade  of  the  affection.  With  the  latter  oljject 
in  view,  the  number  of  red  and  white  cor- 
puscles in  a  given  volume  of  blood — a  cubic 
millimetre — must  be  estimated  bv  means  of  a 


96 

haemacytometer,  such  as  that  of  Gowers  or 
Zeiss.  I  have  more  than  once  refuted  a  di- 
agnosis of  leucocythaemia  which  had  been 
made  by  the  examination  of  a  drop  of  blood 
under  the  microscope.  In  one  of  the  cases  the 
diagnosis  thus  made  seemed  unmistakable, 
but  on  carefully  counting  the  red  and  white 
cells,  I  found  a  great  reduction  of  the  former, 
and  a  proportion  of  one  to  eighty  between  the 
white  and  red,  but  thetiumber  of  the  white  cells 
per  cubic  7nilliineire  was  within  normal  limits.  In 
every  case  of  profound  anaemia  in  which  the 
number  of  white  cells  is  not  reduced /(2r//<a;jjr« 
with  the  red,  the  diagnosis  (?)  of  leucocythaemia 
is  liable  to  be  made,  unless  the  most  accurate 
methods  of  investigation  are  employed.  I  have 
seen  as  many  as  from  twelve  to  fifteen  white 
cells  in  each  microscopic  field  of  a  specimen  of 
blood  of  which  a  more  careful  examination 
showed  that  the  increase  was  merely  relative. 
The  liability  to  error  being  so  great,  what  is  the 
increase,  absolute  and  relative,  which  warrants 
the  diagnosis  of  leucocythaemia  ?  There  is  no 
fixed  rule.  Each  observer  is  a  law  unto  him- 
self. For  my  own  part,  if  the  number  of  leuco- 
cytes per  cubic  millimetre  is  increased  (z.  e.,  if 


97 

they  are  more  than  10,000),  and  if  the  propor- 
tion of  white  cells  to  red  is  as  great  as  one  to 
fifty,  I  consider  that  the  limits  of  leucocytosis 
have  been  overstepped.  This  is  confirmed  by 
the  co-existence  of  great  tenderness  of  sternum, 
ribs  or  vertebras,  and  made  absolutely  certain 
by  the  detection  of  any  enlargement  of  the 
spleen.  As  to  the  question  whether  the  pre- 
cise variety  of  the  disease  may  be  ascertained 
by  an  examination  of  the  blood,  there  is  little 
to  be  said.  As  already  mentioned  under  the 
head  of  changes  in  the  blood,  the  size  of  the 
white  cells  may  vary  greatly  in  the  purely 
splenic  form.  The  presence  of  red  nucleated 
cells  in  the  blood  is  believed  by  Neumann  to  be 
pathognomonic  of  the  medullary  variety,  but 
their  absence  does  not  exclude  an  implication^ 
of  the  marrow.  The  absent  or  diminished 
amoeboid  movement  of  the  white  cells  is  a  point 
with  which  diagnosis  is  not  so  much  concerned 
as  pathogenesis,  and,  therefore,  it  has  been  re- 
ferred to  under  the  latter  head. 

Dr.  Richard  Geigel  {Joe.  cit.)  has  suggested 
and  practiced  the  following  method  for  making 
easier  the  counting  of  the  white  cells.  To  fifty 
cubic  centimetres  of  a  one-half  of  one  per  cent. 

G 


98 

chloride  of  sodium  solution,  are  added  four 
drops  of  a  one  and  one-half  per  cent,  solution 
of  gentian  violet,  and  by  using  this  in  the 
counting  of  the  corpuscles,  instead  of  the  ordi- 
nary diluting  fluid,  the  red  corpuscles  are  un- 
altered, while  the  leucocytes  are  stained  blue, 
so  that  it  is  impossible  to  overlook  a  single  one 
of  them. 

The  diagnosis  of  leucocythaemia  having  been 
made  with  the  microscope,  its  variety  is  to  be 
determined  by  the  ordinary  methods  of  physi- 
cal diagnosis.  A  case  in  which  the  spleen 
is  increased  in  size,  while  nothing  abnormal 
can  be  detected  in  lymph  glands  or  bones,  is 
one  of  pure  splenic  leukaemia.  Combinations 
of  enlarged  spleen  and  lymph  glands  are  desig- 
iiated  as  lieno-lymphatic  or  lymphatico-splenic, 
in  accordance  with  the  supposed  priority  of  the 
organ  affected.  The  medullary  form  may  also 
be  complicated  with  an  enlarged  spleen  or  with 
hypertrophied  lymphatic  ganglia,  and  the  same 
remarks  are  applicable  to  it. 

Prognosis. — In  the  earliest  stage,  that  of  hy- 
peraemia  of  the  haematopoietic  organ  involved, 
a  cure  may  be  effected  by  a  proper  course  of 
treatment.     The  prognosis  is  more  unfavorable 


99 

when  the  enlargement  of  spleen  or  other  organ 
is  maintained  by  numerical  hypertrophy  of 
its  cells,  and  becomes  absolutely  so  when  the 
leukaemic  infection  has  become  general.  The 
latter  event — the  establishment  of  the  leukaemic 
cachexia — may  sometimes  be  demonstrated  by 
an  inspection  of  the  fundus  oculi,  in  which  leu- 
kaemic deposits  are  readily  seen.  A  not  un- 
common m^ode  of  death  is  apoplexy,  to  which 
there  is  a  predisposing  cause  from  malnutrition 
of  vessel  walls,  and  an  exciting  one  from  ac- 
cumulation of  leucocytes  within  their  lumina. 

From  one  to  three  years  is  the  average  dura- 
tion of  the  disease. 

Treatment. — The  cures  reported  have  been 
mostly  in  children,  which  may  be  owing  to  the 
fact  that  their  impressible  systems  render  easier 
an  early  diagnosis.  The  very  fact  that  their 
powers  of  resistance  are  less  than  those  of  adults 
is  thus  favorable,  from  a  therapeutic  stand- 
point. Dr.  Goodhart  has  reported  to  the  Chni- 
cal  Society  of  London  six  cases  of  children, 
under  two  years  of  age,  which  were  cured  by 
the  administration  of  either  phosphorus,  iodide 
of  iron,  or  cod-liver  oil.  In  all  of  them  the 
spleen  was  moderately  enlarged  and  the  white 


100 

cells  increased  about  tenfold.  Mosler  also  has 
reported  the  cure  of  a  boy  of  ten  years,  who 
"  took  adrachmandahalf  of  sulphate  of  quinine 
in  the  course  of  four  days,  and  then  ten  grains, 
and  afterward  six  grains  daily  ;  he  completely 
recovered."  The  case  was  of  the  splenic  form. 
Mosler  prefers  quinine  to  all  internal  remedies, 
but  recommends  also  the  employment  of  oil  of 
eucalyptus  and  piperin,  in  accordance  with  the 
results  of  certain  experiments  by  himself  and 
Hans  Soenderop,  which  show  that  both  these 
substances  cause  contraction  of  the  spleen  in 
dogs.  They  may  be  prescribed  in  pill,  as  in  the 
following  formula : — 

R .     01.  eucalypti,  gtt.  lOO 

Piperini, 

Cerse  albse,  aa  3J 

Pulv.  altheae,  ^ij. 

M.  et  ft.  pil.  No.  C. 

SiG. — Three  to  five  pills  thrice  daily. 

Careful  counts  of  the  blood  corpuscles  during 
the  employment  of  arsenic,  have  proved  that 
this  drug  has  a  favorable  influence  over  the 
course  of  leucocythaemia.  It  should  be  given  in 
full  doses  and  pushed  to  the  point  of  toleration. 
A  local  treatment  of  the  enlarged   spleen  by 


101 

means  of  electricity,  cold  douches,  and  ice  bags, 
has  been  practiced,  and  often  wdth  the  result  of 
materially  reducing  its  size.  Once,  however, 
the  disease  is  fairly  established,  the  spleen  may 
fluctuate  very  greatly  in  size,  without  any  cor- 
responding effect  upon  the  patient's  condition. 
In  the  early  stage  of  the  splenic  form,  local 
treatment  should  not  be  neglected.  Botkin  re- 
ports a  case  of  lieno-lymphatic  leukemia  in 
which  faradization  was  followed  by  a  consider- 
able reduction  in  the  long  and  transverse 
diameters  of  the  enlarged  spleen,  which  coin- 
cided with  improvement  in  the  general  con- 
dition of  the  patient.  In  opposition  it  must  be 
stated  that  Mosler  has  not  been  able  to  confirm 
the  statement  that  the  size  of  the  spleen  is  re- 
duced by  faradization,  but  has  seen  its  long 
diameter  a^/i are/i //y  dimmished  by  being  pushed 
upward  by  the  contraction  of  the  abdominal 
muscles.  Transfusion  of  defibrinated  blood 
has  been  employed  with  marked  temporary 
benefit,  but  cannot  be  regarded  as  a  curative 
measure. 

Extirpation  of  the  spleen  is  only  mentioned 
for  the  purpose  of  condemning  it. 

Postscript. — Although  not  without  an  opinion 


102 

concerning  the  rival  claims  of  Bennett  and  Vir- 
chowtothe  discovery  of  leucocythaemia,  I  have, 
thus  far,  purposely  refrained  from  expressing  it. 
It  appears  to  me  that  the  credit  of  having  pre- 
sented the  subject  of  leucocythaemia  in  such  a 
light  as  to  attract  the  notice  of  the  whole  pro- 
fession, and  to  convince  Bennett  that  six  weeks 
before  he  had  discovered  a  new  disease,  un- 
doubtedly belongs  to  Virchow.  I  also  think  that 
when  a  labored  argument,  such  as  that  of  Ben- 
nett, is  necessary  to  make  good  a  claim,  it  is 
self-evident  that  the  right  of  possession  can  be 
called  in  question. 

ANEMIA   SPLENICA. 

Definition. — This  disease,  which  is  the  splenic 
form  of  pseudoleiikcEmia,  is  completely  ignored 
by  nearly  all  the  numerous  text  books,  hand 
books,  systems  and  cyclopeedias  of  medicine. 
Even  Dr.  Adolph  Striimpell,  who  published  an 
elaborate  article  in  the  Archiv  der  Heilkunde, 
Vol.  XVIII,  1877,  entitled  Ziir  Kentniss  der 
Aiiceniia  Splenica,  devotes  but  eight  lines  to 
this  subject  in  his  recent  text  book  of  medicine. 
Although  apparently  unknown  to  most  of  the 
writers  of  the  works  above  mentioned,  splenic 


103 

anaemia  has  long  been  recognized  as  a  distinct 
affection  by  those  who  have  paid  special  atten- 
tion to  diseases  of  the  haematopoietic  organs. 
For  example,  in  the  course  of  an  article  on  the 
"  Relations  of  LeucocythasmiaandPseudoleukse- 
mia,"  in  the  American  Journal  of  the  Medical 
Sciences  for  October,  1871,  Prof.  Horatio  C. 
Wood  remarks:  "I  now  desire  to  show  that 
there  is  still  a  third  form  of  pseudoleuksemia — a 
splenic  variety.  Under  the  names  of  tumor  of 
the  spleen,  splenic  cachexia,  etc.,  from  time  far 
back,  medical  records  furnish  accounts  of  cases 
which  I  believe  represent  this  affection."  He 
then  proceeds  to  report  a  typical  case  of  anae- 
mia splenica. 

The  best  account  of  this  affection  that  I  have 
been  able  to  find  in  medical  literature  is  by  Dr. 
Guido  Banti  {Annali  Universali  di  Medicijia 
Chirurgia- Parte  Rivisia,  1883),  and  is  based 
upon  a  critical  study  of  three  cases  :  a  woman 
of  73,  a  boy  of  18,  and  a  girl  of  16.  To  it,  as 
well  as  to  the  article  by  Striimpell  above  re- 
ferred to,  I  am  largely  indebted  for  the  follow- 
ing description. 

Anatomical  Characters. — The  cadaver  pre- 
sents the  well-known  appearances  of  extreme 


104 

anaemia,  and  there  is  usually  a  certain  amount 
of  subcutaneous  cEdema  and  serous  effusion. 
The  spleen,  while  retaining  its  shape,  is  en- 
larged, sometimes  to  thrice  its  normal  size  ;  its 
tissue  is  more  or  less  indurated,  and  its  in- 
cisures deeper  than  normal.  The  capsule  pre- 
sents patches  of  thickening  and  opacity,  and  is 
sometimes  adherent  to  neighboring  organs.  On 
the  surface  of  a  section  which  is  of  a  reddish- 
brown  color,  white  or  yellow-white  spots,  usually 
not  exceeding  the  size  of  a  pea,  may  often  be 
observed.  With  the  microscope,  it  is  found 
that  the  normal  adenoid  tissue  has  more  or  less 
completely  disappeared,  its  place  being  more 
than  supplied  by  a  thickening  of  the  reticulum, 
which,  in  parts  of  the  organ,  may  be  so  great  as 
to  form  parallel  bundles  of  fibrous  tissue,  con- 
taining narrow  lacunse,  in  which  are  embedded 
a  few  lymphatic  cells.  The  change  is  precisely 
similar  to  that  of  the  indurated  glands  in  anae- 
mia lymphatica,  and  in  order  to  emphasize  the 
fibrous  character  of  the  alteration  in  both  these 
diseases,  Banti  proposes  for  it  the  name  of 
fibroadenia.  In  the  heart  and  voluntary  mus- 
cles, fatty  changes  are  the  rule.  The  blood 
corpuscles    are    notably     diminished.       From 


105 

5,000,000  per  cubic  millimetre,  they  gradually 
descend  to  four,  three,  or  even  one  million.  In 
a  case  of  my  own  their  number  was  between 
one  and  two  millions.  They  present  the  same 
alterations  in  size  and  shape  as  are  encountered 
in  all  pernicious  forms  of  anaemia.  Notwith- 
standing Banti's  assertion  that  red  nucleated 
cells  have  never  been  observed  in  the  blood  of 
splenic  anemia,  they  are  said,  by  Striimpell, 
to  have  been  numerous,  in  his  case,  in  blood 
from  the  veins  of  the  lungs,  liver  and  spleen. 
They  varied  greatly  in  size  and  shape,  and 
were  mostly  uninuclear,  although  some  con- 
tained two  nuclei,  and  a  few  contained  three. 
With  reference  to  the  proportion  of  white  cells, 
the  cases  may  be  divided  into  two  classes.  In 
the  first,  the  normal  number  of  white  cells  is 
not  surpassed.  In  the  second,  the  white  cells 
are  increased  in  number,  without,  however,  ex- 
ceeding the  limits  of  leucocytosis.  Their  pro- 
toplasm is  granular,  and,  on  the  addition  of 
acetic  acid,  becomes  transparent,  and  shows, 
as  a  rule,  but  one  nucleus.  They  do  not  contain 
pigment  granules,  and,  on  a  warm  stage,  ex- 
hibit well-marked  amoeboid  movements. 

The  marrow   may  present  the  changes  that 


106 

have  been  erroneously  supposed  to  be  peculiar 
to  the  so-called  progressive  pernicious  anaemia. 
In  Striimpell's  case  the  medulla  of  sternum,  ribs, 
and  tibiae,  was  of  a  dark-red  color,  and  of  un- 
usually firm  consistence,  and  presented  the  fol- 
lowing minute  changes:  i.  Scarcely  any  fat 
cells  were  present.  2.  The  colorless  marrow 
cells  were  of  widely  different  size  and  shape, 
mostly  uninuclear,  though  some  contained  two 
nuclei  and  others  enclosed  red  blood  corpuscles. 
3.  Besides  the  ordinary  red  blood  corpuscles, 
there  were  numerous  round,  pale-red,  non- 
nucleated  cells  of  different  size,  and  many  red 
nucleated  cells  of  varying  size  and  shape,  some 
round,  others  elliptic ;  the  former  sometimes 
granular,  the  latter  mostly  homogeneous.  Their 
nuclei  were  often  double,  and  of  the  same  pale- 
red  color  as  the  rest  of  the  cell ;  sometimes  of 
a  more  yellowish  tinge.  Occasionally,  the 
nucleus  was  enlarged  so  as  to  almost  fill  the 
entire  cell ;  often  it  was  placed  eccentrically. 

Clinical  History. — The  disease  may  be  pro- 
perly divided  into  three  stages,  of  which  the 
first,  the  enlargement  of  the  spleen,  is  often 
so  insidious  as  to  pass  for  a  long  time  unob- 
served by  both  patient  and  physician.     It  mani- 


107 

fests  itself  more  frequently  by  a  sense  of  weight 
in  the  left  hypochondrium,  which  may  be  ex- 
perienced only  when  in  the  upright  position. 
Sometimes,  however,  it  gives  rise  to  severe 
neuralgic  paroxysms.  The  second  stage,  that 
of  anemia,  presents  the  phenomena  of  anaemia 
in  general,  such  as  pallor  of  skin  and  mu- 
cous membranes,  dyspnoea,  cardiac  palpitation 
and  fatigue,  on  slight  exertion.  These  symp- 
toms increase  in  severity  until  the  third  stage, 
that  of  cachexia,  is  reached.  The  distinguish- 
ing features  of  this  stage  are  hemorrhage  and 
fever.  The  skin  is  now  the  color  of  yellow  wax ; 
the  muscular  prostration  is  extreme  ;  the  men- 
tal state  is  one  of  hebetude,  and  the  oedema  and 
serous  effusions  increase.  The  adipose  tissue 
generally  disappears  to  a  greater  or  less  extent, 
but  is  sometimes  preserved.  The  disease, 
instead  of  being  continuously  progressive,  may 
recur  in  separate  attacks,  between  each  of  which 
there  may  be  intervals  of  good  health,  of  several 
months'  duration.  This  intermittent  character 
of  the  affection  was  particularly  well  marked  in 
the  case  reported  by  Striimpell,  that  of  a  young 
man,  set.  25,  who,  in  the  course  of  eighteen 
months,  was  the  subject  of  four  attacks  of  pro- 


108 

found  anaemia,  each  of  which  coincided  with 
enlargement  of  the  spleen.  Twice  he  recovered 
from  an  apparently  hopeless  condition.  A  third 
attack  ensued  after  several  months  of  good 
health,  and  he  was  again  improving  when  he 
fell  into  a  state  of  melancholia,  during  which 
the  fourth  attack  occurred  and  was  fatal. 

Careful  examinations  of  the  urine  were  made 
by  Striimpell  in  the  case  referred  to.  It  was 
always  acid,  never  contained  albumin  and, 
notwithstanding  the  icteric  hue  of  the  skin, 
never  responded  to  the  tests  for  bile  pigment. 
Repeated  examinations  showed  that  the  greatest 
destruction  of  albumin  in  the  body,  inferred 
from  the  amount  of  nitrogen  excreted,  coincided 
with  the  worst  periods  of  the  anaemic  attacks. 
This  fact  is  in  perfect  analogy  with  certain 
physiological  experiments  of  Bauer  and  Frankel. 
The  former  found,  after  bleeding  animals,  that 
the  destruction  of  albumin  in  their  bodies  was 
augmented.  The  same  was  true  in  cases  of 
phosphorus  poisoning,  in  which  there  is  de- 
struction of  red  cells.  Frankel  demonstrated 
an  increased  excretion  of  urea  after  any  obstacle 
to  respiration  had  been  placed  in  the  large  air 
passages.     A  similar  increase  had  been  demon- 


109 

strated  in  cases  of  carbonic  oxide  poisoning. 
As  is  well  known,  in  cases  of  CO  poisoning  the 
functional  power  of  the  red  corpuscles  is  para- 
lyzed ;  they  cannot  carry  O  until  the  CO  is  dis- 
placed. In  a  word,  experiments  show  that  any 
cause  which  interferes  with  the  conduction  of 
oxygen  to  the  tissues  may  produce  secondarily 
an  increased  destruction  of  albumin  in  the  body  ; 
and  this  is  found  also  in  states  of  profound 
anaemia  in  which  the  diminished  consumption 
of  O  is  inferred  with  almost  absolute  certainty 
from  the  fact  of  an  enormous  destruction  of  O 
carriers,  and  is  confirmed  by  the  presence  of 
fatty  degeneration  of  heart,  blood  vessels,  etc. 

Nature  of  the  Disease. — Although  ansemia 
splenica  has  been  generally  confounded  with 
other  forms  of  pernicious  ansemia,  there  can  be 
no  question  that  it  constitutes  a  distinct  patho- 
logical entity.  The  enlargement  of  the  spleen 
is  primary,  the  ansemia  secondary ;  as  to  the 
relation  between  them,  there  are  two  hypotheses 
— to  wit :  Either  the  altered  spleen  directly  de- 
stroys the  red  corpuscles,  or  in  it  are  formed 
materials  which  enter  the  circulation  and  inter- 
fere with  the  functions  of  hgematopoiesis.  Of 
these  views,  Banti  espouses  the   latter.     With 


110 

regard  to  the  primary  enlargement  of  the  spleen, 
nothing  is  known.  That  the  disease  is  the  splenic 
form  of  pseudoleukaemia,  is,  according  to  the 
author  just  cited,  proved  by  the  following  facts. 
In  pseudoleuksemia  [i.e.,  anemia  lymphatica, 
or  Hodgkin's  disease),  the  lymphatic  glands  are 
rarely  the  only  organs  affected ;  generally  the 
spleen  is  enlarged  at  the  same  time.  In  some 
cases,  the  enlargement  of  the  spleen  is  in  much 
greater  proportion  than  that  of  the  glands,  and, 
finally,  there  are  cases  (and  these  belong  to  the 
category  of  anaemia  splenica)  in  which  the  spleen 
is  alone  involved. 

The  view  that  this  disease  is  the  splenic  form 
of  pseudoleukaemia  may  be  opposed  on  the 
ground  that  the  morbid  changes  in  the  spleen  in 
anaemia  splenica  are  not  identical  with  those  of 
the  same  organ  when  affected  in  anaemia  lym- 
phatica. In  the  latter  disease,  the  malpighian 
bodies  of  the  spleen,  when  that  organ  is  second- 
arily affected,  are  hypertrophied  to  such  an 
extent  that,  as  I  have  said  under  the  head  of 
"Anaemia  Lymphatica,"  "their white  or  yellow- 
ish color,  like  that  of  the  lymphatic  glands,  con- 
trasted with  the  dark-red  color  of  the  pulp,  gives 
to  the  cut  surface  a   characteristic   variegated 


Ill 

appearance."  This  change  is  beautifully  shown 
in  a  plate  illustrating  an  article  on  Lymphade- 
noma  by  Dr.  Murchison,  in  the  London  Path. 
Sac.  Trans.,  vol.  XXI.  In  marked  contrast  to 
this  description,  the  spleen,  in  the  case  reported 
by  Prof.  H.  C.  Wood,  was  much  enlarged  and 
indurated,  but  the  "  vialpighian  corpuscles  were 
not  at  all  evident.'''  In  summing  up  the  ana- 
tomical characters  of  the  disease,  Banti  says, 
with  reference  to  this  point:  "The  histological 
alterations  of  the  spleen  consist  of  an  atrophy 
and  sclerosis  of  the  itialpighian  corpuscles"  etc. 

These  apparent  discrepancies  may  be  ex- 
plained in  this  manner :  The  spleen  is  not  a 
lymphatic  gland,  but  contains  within  its  pulp 
numerous  bodies — the  malpighian  corpuscles — 
analogous  to  the  lymph  glands.  As  the  latter 
may,  or  may  not,  be  enlarged  in  cases  of  pseu- 
doleuksemia — using  this  term  in  its  broadest 
sense — so  their  analogues  in  the  spleen  may,  or 
7nay  not,  be  enlarged. 

Course  and  Prognosis. — The  duration  of 
splenic  anaemia  is  from  five  or  six  months  to 
three  years.  These  figures  are  certainly  within 
the  mark,  for  in  all  the  cases,  owing  to  the 
insidious  nature  of  the  onset,  more  or  less  of 


112 

the  first  stage  passes  unobserved.  The  disease 
sometimes  occurs  in  separate  attacks,  from  all 
of  which,  except  the  last,  there  may  be  complete 
restoration  to  health ;  and,  on  account  of  this 
peculiarity  in  its  course,  there  is  great  danger  of 
prematurely  reporting  cases  as  cured.  According 
to  Striimpell,  permanent  cures  are  unknown ; 
but  this  opinion  must  be  modified  in  favor  of  a 
few  cases  in  which  splenectomy  has  been  prac- 
ticed successfully. 

Diagnosis. — The  tumor  being  recognized  as 
an  enlarged  spleen,  by  its  situation,  shape  and 
mobility  during  respiration,  the  question  arises 
as  to  the  character  of  the  enlargement.  There 
is  no  difficulty  in  distinguishing  the  tumor  in 
anemia  splenica  from  other  tumors  of  the  spleen 
which  alter  its  normal  shape,  such  as  carcinoma, 
and  echinococci,  but  the  tumors  of  amyloid 
disease,  paludal  cachexia  and  leukaemia  are  to 
be  carefully  differentiated.  Amyloid  disease  is 
secondary  to  suppuration,  especially  in  or  about 
the  bones ;  to  syphilis,  or  to  phthisis,  and  is  not 
confined  to  the  spleen.  It  may  be  demonstrated 
at  the  same  time  in  the  liver,  and  perhaps  also 
in  the  kidney,  by  an  examination  of  the  urine. 
LeukcCmia    splenica    is  excluded  by  a  careful 


113 

count  of  the  white  and  red  cells  ;  and  paludal 
cachexia  by  the  histoiy  of  the  case  and  the 
presence  in  the  blood  of  the  plasmodium  ma- 
lariae, 

A  case  of  ansemia  of  high  grade  associated 
with  a  uniform  splenic  enlargement,  not  mala- 
rial, leuksemic,  or  amyloid,  can  be  no  other  than 
one  of  anaemia  splenica. 

Treatment. — The  medical  means  ofrelief  arethe 
same  as  those  employed  in  other  pernicious  forms 
of  anaemia,  and  have  been,  thus  far,  attended 
with  but  little  success.  Among  them  are  the 
salts  of  quinia,  piperin,  oil  of  eucalyptus,  and 
arsenic.  The  latter  may  be  given  by  the  mouth, 
or  may  be  injected  into  the  splenic  pulp,  as  has 
been  done  with  marked  success  by  Warfwinge, 
in  cases  of  ansemia  lymphatica. 

Faradization  should  be  given  a  thorough  trial; 
for,  even  admitting  that  it  has  no  direct  effect 
upon  the  spleen,  there  is  reason  to  believe  that 
a  salutary  influence  is  exercised  upon  that 
organ  by  the  contraction  of  the  abdominal 
muscles. 

Pain,  vomiting,  diarrhoea,  ascites  and  epistaxis 
are  to  be  treated  in  the  same  manner  as  in  other 
diseases  attended  with  these  symptoms.     Banti 

H 


114 

has  tabulated  the  cases  of  splenectomy  per- 
formed for  non-traumatic  lesions.  They  number 
twenty-one,  of  which  four  were  undoubted 
cases  of  anaemia  splenica.  Of  these  four,  three 
recovered. 

PERNICIOUS   ANiEMIA. 

No7nenclature. — The  term  idiopathic  was  first 
applied  by  Addison  to  certain  cases  of  profound 
anaemia  of  unknown  origin,  w^hich  were  in  all 
respects  identical  with  those  subsequently 
described  by  Biermer,  in  1872,  under  the  title 
of  "  progressive  pernicious  anaemia."  In  the 
latter  term  the  adjective  "  progressive  "  appears 
to  me  not  only  unnecessary  but,  to  a  certain 
extent,  absurd  ;  for  all  diseases  are  progressive 
in  one  or  other  direction.  In  using  the  term 
"idiopathic,"  Addison  was,  no  doubt,  impressed 
with  the  idea  that  when  the  anatomical  basis  of 
a  disease  is  unknown,  it  is  best  to  apply  to  it  a 
title  acknowledging  that  ignorance.  This  I  re- 
gard as  an  error.  It  is  one  thing  to  acknowl- 
edge ignorance  and  another  to  parade  it.  A 
terminology  based  upon  etiology  is  doubtless  the 
most  scientific,  but  one  based  upon  symptoma- 
tology is  not  unscientific.  I  fully  agree  with 
the    late   Dr.    Fagge    that    the    "  phenomena 


115 

which  are  commonly  spoken  of  as  symptoms 
are  part  of  the  disease  to  which  they  belong,  no 
less  than  the  lesion  or  the  specific  cause  or 
whatever  is  taken  as  its  main  characteristic." 
To  those  who  may  think  these  remarks  unnec- 
essary, it  is  a  sufficient  reply  that  our  knowl- 
edge of  the  causes  of  several  forms  of  miscalled 
idiopathic  ansemia  dates  from  the  time  when 
Biermer  substituted  a  significant  symptomatic 
term  for  one  that  had  nothing  but  vagueness  to 
recommend  it. 

Nature  of  Pernicious  Ancemia. — In  placing 
pernicious  anaemia  in  the  category  of  primary 
anaemias,  although  I  do  not  regard  it  as  an 
independent  disease,  I  have  not  been  incon- 
sistent. An  anaemia  becomes  pernicious  when 
the  blood  corpuscles  undergo  a  series  of 
changes  which  cause  them  to  resemble,  in 
more  than  one  respect,  the  corpuscles  of  th-e 
amphibia.  Pernicious  anaemia  is  the  final 
stage  of  several  forms  of  symptomatic  anaemia 
and  of  chlorosis.  The  prognosis  of  anaemia 
per  se  is  good  until  the  changes  in  the  blood 
corpuscles  above  referred  to  are  manifest. 

I  cannot  better  explain  my  views  with  refer- 
ence to  this  afi'ection  than  by  quoting  from  an 


116 

article  that  I  contributed  to  the  Philadelphia 
Medical  Times  for  April  3d,  1886.  "  The  most 
interesting  fact  in  connection  with  the  exami- 
nation of  the  blood  of  pernicious  ansemia,  and 
one  to  which,  so  far  as  I  know,  attention  has 
never  been  particularly  directed,  is  that  it 
demonstrates  a  reversion  to  the  type  of  blood 
found  in  the  lower  animals.  This  might  be 
justly  regarded  as  a  fanciful  idea  if  it  were  based 
upon  a  resemblance  of  the  blood  of  pernicious 
anaemia  to  that  of  the  lower  animals — birds, 
fishes,  reptiles — in  any  one  particular ;  but  I 
propose  to  show  that  the  red  corpuscles  in  this 
disease  approach  those  of  the  lower  animals  in 
many,  if  not  in  all,  of  their  chief  characteristics  ; 
namely,  in  their  number,  their  size,  their  shape, 
and  the  amount  of  haemoglobin  they  carry." 
After  giving  some  details  concerning  the 
blood  corpuscles  of  the  lower  vertebrate  ani- 
mals and  their  percentage  of  haemoglobin,  I 
continued  as  follows:  "Turning  from  these 
interesting  facts  of  comparative  physiology  to 
their  bearing  upon  the  subject  of  this  paper, 
we  observe  in  well-marked  cases  of  pernicious 
anaemia:  i.  A  reduction  in  the  number  of  the 
red  corpuscles  to  a  degree  that  is  normal  in  the 


117 

cold-blooded  animals.  It  is  not  at  all  uncommon 
to  find  in  this  disease  less  than  1,000,000  corpus- 
cles per  cubic  millimetre.  My  lowest  counts 
have^  been  525,000  five  days  before  death ; 
560,000  in  a  case  in  which  recovery  took  place  ; 
and  315,000  a  few  hours  before  death.  In  the 
celebrated  case  of  Quincke  there  were  but 
143,000  per  cubic  millimetre,  and  yet  the 
patient  recovered.  Figures  like  these  are,  as 
has  just  been  said,  normal  in  the  cold-blooded 
animals.  2.  In  pernicious  anaemia  the  propor- 
tion of  haemoglobin  is  often  much  greater  than 
normal.  It  has  been  observed  by  Laache  and 
others  to  be  double  the  normal  amount.  This, 
in  the  opinion  of  the  writer,  is  the  most  remark- 
able feature  of  this  disease,  distinguishing  it 
from  all  other  forms  of  anemia,  and  is  due  to 
the  fact  that — 3,  many,  sometimes  the  majority, 
of  the  corpuscles  are  greatly  increased  in  size. 
This  is  well  seen  in  the  accompanying  cuts, 
from  photo-micrographs  of  diseased  and  normal 
blood,  made  for  me  by  Mr.  W.  H.  Walmsley, 
of  this  city.  The  photographs  of  the  two  speci- 
mens were  made  under  precisely  similar  opti- 
cal conditions.  The  patient  furnishing  the 
diseased  specimen  of  blood  is  a  typical  case  of 


119 

pernicious  anaemia,  and  is  still  under  my  obser- 
vation.* 

"  By  applying  the  points  of  a  pair  of  compasses 
to  the  enlarged  corpuscles,  it  will  be  proved  that 
many  of  them  are  at  least  double  the  normal 
size.  4.  The  corpuscles  are  not  only  increased 
in  diameter,  but  altered  in  shape,  and  have  a 
decided  tendency  to  assume  an  oval  outline. 
So  much  so  that,  in  measuring  them  in  the 
manner  indicated,  we  have  to  take  into  con- 
sideration the  direction  in  which  the  measure- 
ment is  made.  They  have  a  long  a?id  a  short 
diameter  y 

The  specimen  from  which  the  above  cut 
was  taken  was  not  selected  with  the  view  of 
upholding  this  theory  of  reversion,  but  may  be 
regarded  as  typical  of  the  corpuscles  of  per- 
nicious anaemia.  The  enormous  size  of  the  cor- 
puscles (megalocytes)  and  their  altered  shape 
are  still  better  shown  in  a  cut  in  the  work  of 
Laache  {^Die  Anceinie),  who  had  no  theory  of 
reversion  to  maintain. 

From  the  standpoint  of  the  blood  changes 
and  of  the  clinical  history,  I  contend  that  per- 
nicious ansemia  is  a  condition  that  may  result 

*  He  has  since  died. 


120 

from  a  number  of  causes.  Prominent  amono: 
these  is  atrophy  of  the  stomach.  In  the  Ameri- 
can Jour  7ial  of  Medical  Sciences,  April,  1886,  I 
reported,  in  conjunction  with  Prof.  Wm.  Osier, 
a  typical  case  of  pernicious  anaemia  in  which 
the  only  special  lesion  was  atrophy  of  the  mu- 
cous membrane  of  the  stomach.  "  This  was 
evident  to  the  naked  eye  in  the  thin,  cuticular 
appearance,  and  was  abundantly  confirmed  by 
the  microscopical  examination,  which  showed 
that  the  peptic  glands  had  been  destroyed  over 
the  greater  portion  of  the  organ."  About  the 
same  time  I  had  under  observation  another  case, 
a  lady,  whose  symptoms  and  blood  changes 
were  identical  with  those  of  the  above  mentioned 
case.  After  an  illness  of  more  than  a  year  she 
died,  and  at  the  autopsy,  at  which  I  was  present, 
no  lesion  was  found  to  explain  the  profound 
alteration  of  the  blood.  According  to  most 
authorities,  the  first  of  these  cases  in  which  a 
lesion  was  found,  to  which  the  symptoms  might 
be  reasonably  attributed  is,  for  that  very  reason, 
not  a  case  of  pernicious  anaemia.  The  second 
case,  on  the  other  hand,  is  a  case  of  pernicious, 
or  "  idiopathic,"  anaemia  because  a  lesion,  to 
which  the  symptoms  might  be  attributed,  was 


121 

not  found.  This  appears  to  me  to  be  a  very- 
unscientific  mode  of  considering  this  subject. 
Little  by  little,  causes  have  been  discovered  suffi- 
cient to  account  for  all  the  symptoms  of  many- 
cases  of  idiopathic  anaemia.  One  of  the  latest 
contributions  of  this  sort  has  been  that  of  Dr.  Gus- 
tav  Reyher  {Detdsches  Archiv  fur  Klin.  Med., 
Bd.  xxxix),  who  reports  thirteen  cases  of  profound 
ansemia  caused  by  an  intestinal  parasite,  the 
bothriocephalus  latus.  In  all  their  features, 
these  cases  deserve  the  name  of  pernicious,  and 
had  they  been  fewer  in  number  and  treated 
in  a  different  manner,  the  anaemia  might  have 
been  considered  "idiopathic,"  the  presence  of 
a  tapeworm  in  the  intestine  being  regarded,  in 
a  country  where  this  parasite  is  not  uncommon, 
as  a  mere  coincidence.  The  proof  that  the 
anaemia  was  secondary  and  parasitic  was  fur- 
nished by  the  fact  that,  in  every  instance,  a 
wonderfully  rapid  recovery  from  an  apparently 
hopeless  condition  followed  the  expulsion  of 
the  worm.  From  such  facts  as  these  it  is  reason  - 
able  to  conclude  that  our  ignorance  concerning 
the  cause  of  the  most  obscure  forms  of  perni- 
cious anaemia,  and  our  expression  of  that  igno- 
rance by  the  term  "idiopathic,"  will  gradually 
disappear. 


122 

Having  stated  above  that  I  do  not  regard 
pernicious  ansemia  as  an  independent  disease, 
some  explanation  is  needed  of  my  reasons  for 
classifying  it  under  the  head  of  primary  anae- 
mias. I  have  none  better  than  the  one  already 
given  by  me  in  the  course  of  an  article  in  the 
Medical  News  for  July  3d,  1886  : — 

"  Opinions  are  divided  as  to  whether  per- 
nicious anemia  is  due  to  the  operation  of  a 
cause  (unknown)  sui  generis,  or  to  the  pro- 
longed operation  of  the  ordinary  causes  of  anae- 
mia. The  writer  is  of  the  opinion  that  the 
varied  clinical  history  of  the  different  cases  on 
record  furnishes  most  decided  evidence  in  favor 
of  the  latter  view.  Anaemia,  once  established, 
tends  to  perpetuate  itself  in  that  species  of 
vicious  circle  of  which  so  many  examples  are 
furnished  by  pathology.  Thus,  to  take  an  ex- 
treme example,  the  epileptiform  convulsions 
which  immediately  precede  death  from  hemor- 
rhage are  due  to  cerebral  ischaemia,  and  this 
very  ischaemia  is  increased  by  the  convulsions, 
for  experiments  have  shown  that  the  voluntary 
muscles  contain  a  much  greater  amount  of 
blood  during  contraction  than  while  at  rest.  It 
is  quite  as  essential  to  the  blood-making  organs 


123 

as  it  is  to  the  nerve  centres  that  they  be  properly 
supplied  with  blood,  in  order  that  they  may  act 
their  important  part  toward  maintaining  the 
bodily  health.  Doubtless  there  are  reserve 
powers  and  compensatory  activities  in  each  and 
all  of  the  blood-making  organs,  which  may 
suffice  to  furnish  a  fair  quality  of  blood  under 
the  most  adverse  circumstances.  These  powers, 
however,  have  their  limit,  and,  once  exhausted, 
the  anaemia,  instead  of  continuing  'simple,' 
'  functional,'  or  '  symptomatic,'  becomes  '  essen- 
tial,' '  oiganic,'  or  '  pernicious.'  " 

In  short,  I  consider  some  forms  of  pernicious 
anaemia  to  be  due  to  malnutrition  of  the  cyto- 
genetic organs. 

Symptoms. — In  the  words  of  Coupland,  "the 
symptoms  of  pernicious  anaemia  are  those  of 
simple  anaemia  aggravated  and  intensified." 
In  well-marked  cases  the  appearance  of  the 
patient  is,  to  a  certain  extent,  diagnostic.  The 
lips  and  palpebral  conjunctiva  are  of  a  milky 
white  color  and  the  skin  of  a  lemon  tint.  This 
hue  of  the  skin  is  characteristic,  and  at  once 
gives  rise  to  the  suspicion  of  pernicious  anaemia 
to  those  who  have  seen  one  or  more  cases  of 
the  disease.     It  is  unnecessary  to  enter  at  length 


124 

into  the  symptoms  of  this  affection  which  are, 
for  the  most  part,  dependent  upon  want  of 
oxygen.  The  chief  of  them  are  extreme  muscu- 
lar prostration,  breathlessness  and  syncope  on 
slight  exertion,  or  even  in  raising  the  head  from 
the  pillow  ;  and  digestive  disturbances,  such  as 
anorexia,  nausea  and  vomiting,  and  constipa- 
tion alternating  with  diarrhoea.  Insomnia  is 
more  frequent  than  drowsiness  until  toward  the 
end,  when  somnolence  gradually  deepens  into 
lethargy  and  coma.  Physical  examination,  in 
typical  cases,  reveals  nothing  but  anaemic  mur- 
murs over  the  heart,  most  distinct  at  the  base 
and  the  bruit  de  diable  in  the  veins  of  the  neck. 
The  pulse  is  usually  rapid,  from  loo  to  120. 
The  bones,  particularly  the  sternum,  are  often 
tender  on  percussion.  Retinal  hemorrhages  are 
found  in  the  majority  of  cases.  The  blood  is 
not  only  of  the  poorest  quality,  but  is  so  small 
in  quantity  that  often  a  drop  is  squeezed  with 
great  difficulty  from  a  deep  puncture  in  the 
finger  pulp.  It  resenlbles  serum  more  than 
blood,  and  is  aptly  compared  to  water  in  which 
beef  has  been  washed.  On  examination  with 
the  microscope,  the  corpuscles  present  great 
diversities  in  size  and  shape.     The  majority  are 


125 

often  much  larger  than  normal,  and,  compared 
with  normal  corpuscles,  are  worthy  of  the  name 
of  Jiiegalocytes.  Others  are  much  below  the 
normal  size,  and  are  called  microcytes ;  while 
others  are  greatly  distorted,  being  pear-shaped 
for  the  most  part,  but  sometimes  biscuit-shaped, 
hammer-shaped,  or  anvil-shaped.  These  last 
are  known  2^'=,  poikilocytes.  The  percentage  of 
haemoglobin,  owing  to  the  increased  size  of  the 
corpuscles,  is  often  as  great  as,  or  greater  than, 
normal,  sometimes  attaining  twice  the  normal 
proportion.  This  abnormal  proportion  of  hae- 
moglobin is  not  always  due  to  the  increased 
size  of  the  corpuscles  alone  ;  for,  in  some  cases, 
the  blood  contains  a  large  number  of  minute, 
highly-colored  globules,  which  Eichhorst  re- 
garded as  pathognomonic.  They  are  so  minute 
as  to  look  like  "  small,  red-tinged,  fat  globules." 
These  bodies  are,  of  course,  not  counted  in  esti- 
mating the  number  of  the  red  corpuscles,  and 
yet  their  coloring  matter  contributes  to  the  esti- 
mate of  the  percentage  of  haemoglobin.  The 
corpuscles  are,  therefore,  sometimes  credited 
with  more  coloring  matter  than  they  possess. 
These  minute  colored  bodies  are  not  always 
present.     I  have  met  with  them  in  but  one  case. 


126 

and  Dr.  Grainger  Stewart  was  unable  to  find 
them  in  two  well-marked  and  ultimately  fatal 
cases  which  occurred  in  his  practice.  Fever 
of  irregular  type  is  certain  to  occur  in  late 
stages  of  pernicious  anaemia.  It  has  already 
been  spoken  of  among  the  symptoms  of  anaemia 
in  general.  An  increased  excretion  of  nitrogen 
by  the  kidneys  has  been  demonstrated  in  this 
affection  by  Striimpell,  and  is  due  to  the  inade- 
quate supply  of  oxygen  to  the  tissues.  This 
fact  is  of  interest  in  connection  with  the  exten- 
sive fatty  degeneration,  which  is  sometimes  the 
only  lesion  detected  in  this  disease.  "  The  fat 
represents  the  non-nitrogenized  remnants  of  the 
decomposed  albuminoids." 

Anatomical  Characters.  —  These  are  the 
changes  in  the  blood  itself  and  the  consecutive 
lesions  in  other  tissues.  The  former  have  been 
already  described  and  figured  in  the  course  of 
this  section  Of  the  latter,  the  fatty  degenera- 
tions of  heart,  intima  of  blood  vessels,  gastric 
tubules,  etc.,  are  mentioned  under  the  head  of 
anatomical  characters  of  anaemia  in  general. 
In  1875,  Prof.  William  Pepper  suggested  the 
marrow  as  the  source  of  the  blood  lesions  of 
pernicious    anaemia,    and   "  described   definite 


127 

changes,  chiefly  of  small,  granular  cells,  in  the 
marrow  of  the  radius  and  sternum  in  one  case." 
The  marrow  in  this  case,  the  first  in  which  a 
careful  examination  of  this  tissue  was  made,  is 
described  as  "decidedly  paler  than  in  health." 
This  is  not  the  appearance  of  the  hyperplasia 
of  the  marrow,  which  is  regarded  by  some  as 
the  fundamental  lesion  of  this  affection.  The 
marrow  is  of  a  reddish  purple  color  ;  its  consist- 
ence is  increased ;  its  fat  cells  have  disap- 
peared, and  the  specific  cellular  elements  of  the 
medulla  have  increased  in  amount.  Frequently, 
also,  large  numbers  of  nucleated  red  corpuscles 
are  found.  These  changes,  interesting  and  sug- 
gestive though  they  be,  are  by  no  means  pecu- 
liar to  pernicious  anaemia  and,  when  present, 
are  not  primary.  They  maybe  entirely  absent, 
as  in  a  thoroughly  studied  case  reported  by  Dr. 
J.  H.  Musser,  of  Philadelphia.  They  may  also 
be  present  in  other  diseases.  They  were  found 
by  Litten  in  four  cases  of  uterine  carcinoma, 
and  by  Oi?th  in  a  case  of  carcinoma  recti,  and 
in  another  of  carcinoma  mammae.  {^Berlin 
Klin.  Wochensch.,  xiv,  748.) 

Diagnosis. — In    accordance  with   the   views 
here  presented,  an  anaemia  has  entered  upon 


128 

the  pernicious  stage  when  the  blood  corpuscles 
are  greatly  diminished  in  number  —  below 
2,000,000  per  cubic  millimetre — and  have  under- 
gone the  alterations  in  size  and  shape  already 
described  and  figured.  In  addition,  the  per- 
centage of  haemoglobin  may  be  normal  or 
above  normal ;  certainly  but  little  below  it  in 
any  case.  A  blood  containing  megalocytes, 
poikilocytes  and  microcytes,  is  the  blood  of 
pernicious  anaemia.  This  condition  may  be 
secondary,  i.  e.,  the  cause  is  known  ;  or  primary, 
z.  <?.,  the  cause  is,  as  yet,  unknown. 

Prognosis. — The  prognosis  of  pernicious  anae- 
mia is  unfavorable,  but  there  are  brilliant  excep- 
tions to  this  rule  ;  for  example,  those  furnished 
by  Reyher's  cases.  These  were,  doubtless, 
from  an  etiological  standpoint,  cases  of  parasitic 
anaemia,  but  clinically  they  presented  every 
feature  of  pernicious  anaemia.  In  general  terms, 
when  the  cause  is  known  and  removable,  the 
prognosis  is  good ;  when  known  and  not  re- 
movable, it  is  hopeless  ;  when  unknown,  it  is 
doubtful. 

Treatment. — Confining  what  is  to  be  said 
about  treatment  to  those  cases  in  which  the 
cause  is  unknown,  the  best  results  have  been 


129 

attained  by  the  use  of  arsenic,  iron,  and  quinine. 
Numerous  undoubted  cures  have  followed  the 
use  of  the  first  of  these  drugs,  which  may  be 
given  in  pill  or  in  Fowler's  solution.  Trans- 
fusion has  been  attended  with  little  or  no  suc- 
cess, but  Dr.  Oscar  Silbermann  reports  two 
cases  of  profound  ansemia  which  recovered 
after  subcutaneous  injections  of  defibrinated 
blood.  The  blood  was  injected  under  strict 
antiseptic  precautions,  and  the  quantity  of  each 
dose  varied  from  twenty  to  forty  grammes.  In- 
halations of  oxygen  and  the  subcutaneous  in- 
jection of  quinine  are  recommended  by  Dr. 
Henrot  of  Rheims.  Of  equal  importance  with 
drugs,  is  a  nutritious  diet,  of  which  the  digestion 
may  be  assisted  by  malt  and  pancreatic  extract 
or  the  food  may  be  peptonized  before  its  inges- 
tion. 

SECONDARY   AX.CMIA. 

As  already  remarked  on  a  previous  page, 
"  Nearly  every  morbid  process,  when  it  occurs 
in  a  severe  form,  is  sooner  or  later  followed  by 
anaemia."  It  is  therefore  impossible,  within  the 
limits  of  this  work,  to  consider  every  form  of 
secondary  anaemia.  It  is  also  unnecessary,  for 
I 


130 

the  differences  between  the  various  forms  are 
those  of  degree,  not  of  kind. 

The  anaemias  of  fever  and  hemorrhage  have 
already  been  considered.  That  of  syphilis  has 
been  studied  by  Wilbouchewitch ;  by  Keyes,  of 
New  York,  and  by  Laache,  of  Christiania,  and 
it  has  been  demonstrated  that  the  improvement 
which  follows  the  administration  of  mercurials 
is  accompanied  with  an  increase  in  the  number 
and  value  of  the  red  corpuscles.  In  the  ad- 
vanced stages  of  phthisis,  cancer,  Bright's  dis- 
ease, and  cirrhosis  of  the  liver,  the  blood 
corpuscles  are  greatly  reduced  in  number — be- 
tween 2,000,000  and  3,000,000 — and  may  assume 
the  characters — increased  size  and  altered  shape 
— of  pernicious  anaemia. 

TOXANiEMIA. 

A  poison  may  produce  anaemia  either  directly 
or  indirectly.  The  ingestion  of  arsenic  and 
phosphorus,  and  the  inhalation  of  arseniureted 
hydrogen  are  directly  followed  by  the  destruc- 
tion of  red  corpuscles  in  such  quantities  that 
haemoglobin  appears  in  the  urine,  and  even 
jaundice  (haematogenous)  may  ensue.  In 
certain  susceptible  individuals  the  same  symp- 


131 

toms  are  caused  by  prolonged  exposure  to  cold. 
Other  substances,  such  as  potassium  chlorate 
and  certain  edible  fungi,  morchella  andhelvella, 
esculenta,  produce  the  same  effects.  For  details 
concerning  these  and  other  agents  destructive 
to  the  red  corpuscles,  the  reader  is  referred  to 
my  article  on  "  Hsemoglobinuria,"  in  "  Wood's 
Reference  Handbook  of  Medicine."  The  action 
of  lead  upon  the  blood  corpuscles  is  probably 
altogether  indirect,  through  the  marked  disturb- 
ances of  digestion  to  which  it  gives  rise.  A 
decided  degree  of  ansemia  in  a  case  of  chronic 
lead  poisoning  should  lead  to  a  careful  examina- 
tion of  the  urine ;  for,  as  is  well  known,  the  long- 
continued  ingestion  of  lead  is  one  of  the  causes 
of  cirrhotic  kidney. 

The  anaemia,  if  such  it  can  be  called,  pro- 
duced by  carbonic  oxide  poisoning,  differs  from 
all  other  forms  of  toxanaemia.  This  gas,  when 
inhaled,  "displaces  the  oxygen  of  the  blood- 
coloring  matter,  and  takes  its  place,  molecule  for 
molecule.  The  combination  thus  formed  is  re- 
markable for  its  stability,  although,  contrary  to 
what  was  formerly  supposed,  it  can  be  displaced 
by  an  indifferent  gas  or  in  a  vacuum.  Its  crys- 
tals are  isomorphous  with  those  of  oxy-haemo- 


132 

globin,  but  have  a  slight  bluish  tinge.  Its 
spectrum  is  almost  identical  with  that  of  O-hse- 
moglobin,  but  the  two  absorption  bands  are 
moved  very  slightly  nearer  the  violet  end."''^ 
The  effect  of  this  gas  is  to  pm-alyze  the  red  cor- 
puscles which,  until  it  is  displaced,  are  incapable 
of  performing  their  functions.  The  symptoms 
of  this  form  of  toxanasmia  are  coma,  with  ster- 
torous respiration,  pallor  and  coolness  of  the 
skin,  while  the  mucous  membranes  are  bright 
red;  rigidit}^  of  muscles,  dilated  pupils  and 
usually  a  slow,  easily-compressible  pulse.  The 
symptoms  are,  however,  not  uniform  ;  for  cases 
are  reported  in  which  there  was  no  stertor,  the 
pulse  was  small  and  quick  and  the  pupils  con- 
tracted. Convalesence  is  apt  to  be  very  slow. 
In  a  case  reported  by  Dr.  John  Graham  in 
the  "Transactions  of  the  College  of  Physicians 
of  Philadelphia,"  series  iii,  vol.  viii,  the  patient, 
a  woman,  aet.  74,  was  not  able  to  sit  up  until 
seventy-three  days  after  the  accident. 

PARASITIC    ANEMIA. 

The  parasites  which  have  been  thus  farrecog- 

*Articleon  Blood,  in  "  Wood's  Reference   Handbook,"  by 
F.  P.  Henry. 


133 

nized  as  causative  of  anasmia  are  the  anchy- 
lostomum  duodenale,  the  bilharzia  hsematobia, 
the  filaria  sanguinis,  the  bothriocephalus  latus, 
and  perhaps,  also,  the  plasmodium  malarise. 

The  anchylostomum  duodenale  was  first 
recognized  by  Griesinger,  in  1854,  as  the  cause 
of  a  profound  endemic  anasmia,  known  as 
Egyptian  chlorosis.  Since  then  it  has  attacked 
the  Italian  laborers  employed  in  the  construction 
of  the  St.  Gothard  tunnel,  and  has  also  prevailed 
among  brickmakers  in  Germany.  The  bilharzia, 
first  discovered  by  Bilharz  in  Egypt,  in  185 1, 
gives  rise  to  anasmia  by  the  hsematuria  caused 
by  its  presence  in  the  body.  The  adult  animals 
lie  in  dilated  blood  vessels  in  the  neighborhood 
of  the  bladder  or  other  urinary  outlet,  and  the 
symptoms  are  due  to  the  interference  with  the 
circulation  and  the  irritation  caused  by  the  ova 
on  their  way  to  the  urinary  passages.  The 
filaria  sanguinis  causes  ansemia  by  interfering 
with  the  lymphatic  circulation.  The  obstruction 
to  the  lymph  vessels  may  be  so  great  as  to  lead 
to  their  rupture,  in  which  event  the  lymph 
escapes  from  the  body,  usually  with  the  urine 
(chyluria) ;  sometimes,  however,  directly  from 
the  integument,  as  in  cases  of  lymph-scrotum. 


134 

This  parasite  is  quite  common  in  certain  tropical 
and  subtropical  countries,  especially  in  China, 
and  has  recently  acquired  a  new  interest  from 
the  discovery,  by  Dr.  John  Guiteras,  of 
Charleston,  S.  C,  that  it  is  indigenous  to  the 
United  States.* 

The  Plasmodium  malarise  is  the  hasmatozoon 
discovered  by  Laveran  in  Algiers.  It  exists 
within  the  red  corpuscles  and  free  in  the  blood, 
and  is  probably  operative  in  the  causation  of 
malarial  anaemia.  This  organism  has  been 
studied  by  several  careful  observers ;  in  this 
country  particularly  by  Councilman,!  of  Balti- 
more, and  Osler,J  of  Philadelphia,  although,  to 
quote  the  latter,  "  Laveran's  original  descrip- 
tion is  well  nigh  complete,  and  subsequent 
workers  have  done  little  else  than  confirm  his 
results,  though  to  Marchiafava  and  Celli  is  due 
the  credit  of  insisting  upon  the  amcEboid  char- 
acter of  the  intra-cellular  form." 

*  Medical  News,  April  loth,  1886. 

f "  Transactions    of   the  Association    of  American    Physi- 
cians," vol.  i. 
X  British  Medical  Journal ,  March  12th,  1887. 


INDEX. 


PAGES 

Ansematosis, ?4,  69 

Ansemia,  predispositions  to, 16,  17 

senile, 18 

congenital,      18 

from  hemorrhage, 22 

latent, 25 

lightest  grade  of, 31 

highest  grades  of, 33 

classification  of, 46 

lymphatica,  synonyms  of, 59 

infective  nature  of, ' 65 

nature  of, 69 

symptoms  of, 70 

diagnosis  of, 72 

prognosis  of 73 

treatment  of, 74 

splenica, 102 

anatomical  characters  of, 103 

clinical  history  of, 106 

nature  of, 109 

course  and  prognosis  of, iii 

diagnosis  of, 112 

treatment  of, 113 

Blood-plates, 6 

Chlorosis, 47 

confused  ideas  concerning, 51 

diagnosis  of, 54 

prognosis  of, 57 

treatment  of, 58 

Compte-globules  of  Malassez,      11 

Corpuscles,  red, i,  2 

white, 4 

Fibroadenia, 104 

Globinometer, 14 

135 


136  INDEX. 


PAGES 

Hsemacytometer, ii,  12 

Hsematoblasts, 6 

Hsemic  unit,      54 

Haemoglobin, 2 

Hayem's  formula  for  intra-venous  injection, 42 

Hematimetre, 11 

Leucocrystallin, 85 

Leucocythsemia, 75 

nomenclature  of, 75 

anatomical  characters  of, 76 

retinal  changes  in, 81 

blood  changes  in, 82 

clinical  history  of, 85 

pathogenesis  of, 88 

lymphatic,  a  "  myth^" 92 

aetiology  of, 94 

diagnosis  of, 95 

prognosis  of, 98 

treatment  of, 99 

Leucocj'tosis, 76 

Leukosin, 84 

Microcytes, 7 

Parasitic  anaemia, 132 

Pernicious  anaemia, 114 

nature  of, 115 

symptoms  of, 123 

anatomical  characters  of, 126 

diagnosis  of, 127 

prognosis  of, 128 

treatment  of, 128 

Poikilocytosis, 34 

Pseudochlorosis, 50 

Schultze's  granule  masses, 6 

Secondary  anaemia, 129 

Toxansemia, 130 

Transfusion, 41 


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1012  Walnut  Street,  Philadelphia. 


Catalogues. 

p.  Blakiston,  Son  &  Co.,  Medical  Publishers, 
No.  IOI2  Walnut  Street,  Philadelphia,  will  send  the 
following  Catalogues,  free,  to  any  address,  upon 
application: — 

A  Descriptive  Catalogue  of  all  their  Publications, 
with  a  Subject  Index, 

A  Catalogue  of  Books  for  Dental  Students  and  Prac- 
titioners. 

A  Catalogue  of  Books  on  Chemistr}',  Pharmacy,  Mi- 
croscopy, Hygiene,  Health,  and  other  scientific 
subjects. 

A  Catalogue  of  books  more  especially  for  Students, 
including  the  ?  Quiz-Compends.  ? 

A  Complete  Classified  Catalogue  of  all  Books  on 
Medicine,  Dentistry,  Pharmacy  and  Collateral 
Branches. 

A  Catalogue  of  Periodicals  with  Club  Rates. 


"^C<i'^V 


K^ 


